БЕТА-L-2' ДЕЗОКСИНУКЛЕОЗИДЫ ДЛЯ ЛЕЧЕНИЯ ГЕПАТИТА В

Данное изобретение относится к лекарственным средствам для лечения хозяина, инфицированного вирусом гепатита В, содержащим соединения указанных структурных формулы или к их фармацевтически приемлемым солям. Кроме того, изобретение относится к фармацевтическим композициям для лечения хозяина, инфицированного вирусом гепатита В, на основе каждого из данных соединений в отдельности (или их фармацевтически приемлемой соли), а также в их комбинации с эффективным количеством соединения, выбранного из группы, состоящей из β-L-2-гидроксиметил-5-(цитозин-1-ил)-1,3-оксатиолана (3ТС), цис-2-гидроксиметил-5-(5-фторцитозина-1-ил)-1,3-оксатиолана (FTC), β-L-2'-фтор-5-метил-арабинофуранозил-уридин (L-FMAU), β-D-2,6-диаминопуриндиоксолана (DAPD), фамцикловира, пенцикловира, 2-амино-1,9-дигидро-9-[4-гидрокси-3-(гидроксиметил)2-метиленциклопентил]-6Н-пурин-6-она (энтекавир, ВMS-200475), 9-[2-(фосфоно-метокси)этил]аденина (РМЕА, адефовир, дипивоксил), лобукавира, ганцикловира и рибавирина. 6 н. и 6 з.п. ф-лы ...

НОВЫЕ БИЦИКЛИЧЕСКИЕ НУКЛЕОЗИДЫ И ОЛИГОМЕРЫ, ПОЛУЧЕННЫЕ ИЗ НИХ

Изобретение относится к новым соединениям формулы (I) и олигонуклеотидам, полученным из них. В частности, настоящее изобретение относится к соединению формулы (I) где один из T1 и Т2 представляет собой OR1 или OR2; и другой из T1 и Т2 представляет собой OR1 или OR2; где R1 представляет собой Н или гидроксил-защитную группу, где указанная гидроксил-защитная группа независимо в каждом случае выбрана из ацетила, бензила, трет-бутилдиметилсилила, трет-бутилдифенилсилила, тритила, 4-монометокситритила, 4,4'-диметокситритила (DMTr), 4,4',4''-триметокситритила (TMTr), 9-фенилксантин-9-ила (пиксила) и 9-(п-метоксифенил)ксантин-9-ила (МОХ), и R2 представляет собой фосфорсодержащий фрагмент, где указанный фосфорсодержащий фрагмент представляет собой фосфорамидитный фрагмент, представленный формулой (X) где R5 представляет собой С1-С9 алкил, замещенный циано; R6 и R7 независимо представляют собой С1-С9 алкил; или совместно с атомом азота, к которому они присоединены, образуют гетероциклическое кольцо ...

СПОСОБ СИНТЕЗА БЕТА-L-5-ФТОР-2', 3'-ДИДЕЗОКСИ-2',3'-ДИДЕГИДРОЦИТИДИНА (БЕТА-L-FD4C)

Изобретение относится к способу получения β-L-5-фтор-2',3'-дидезокси-2',3'-дидегидроцитидина (β-L-FD4C), который используется в качестве противовирусного агента. Этот способ может быть применен в крупномасштабном производстве β-L-FD4C и является эффективным, высокоэкономичным и экологически приемлемым. 22 з.п. ф-лы. 1 табл. 1 ил.

2,6-ДИНИТРОСОДЕРЖАЩИЕ ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ПУРИНА, СПОСОБ ИХ ПОЛУЧЕНИЯ И ИСПОЛЬЗОВАНИЕ

Настоящее изобретение относится к противоопухолевым производным пурина формулы (А) и их солям, а также фармацевтическим композициям на их основе, способу их получениягде W обозначает алкилзамещенный амино, остаток пирролидина, пиперидина, морфолина или пиперазина, необязательно замещенный С-Салкилом или гидрокси; Y обозначает Н или остаток сахарида, Z обозначает Н; Q обозначает остаток необязательно замещенного хинолина. Предложены новые соединения с низкой токсичностью, широким противораковым диапазоном, высокой противораковой активностью, высокой стабильностью, пригодные для изготовления противоопухолевых лекарственных средств. Предложенный способ состоит во взаимодействии защищенного по 9-му положению соответствующего пурина с соответствующими предшественниками групп W и Q. 4 н. и 8 з.п. ф-лы, 3 табл., 31 пр.

ПРОИЗВОДНЫЕ 2,6-ДИАМИНОПУРИН-β-D-РИБОФУРАНУРОНАМИДА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМСОСТАВ ДЛЯ ПОДАВЛЕНИЯ АКТИВНОСТИ ЛЕЙКОЦИТОВ, СПОСОБ ЕГО ПОЛУЧЕНИЯ, СПОСОБ ПОДАВЛЕНИЯ АКТИВНОСТИ ЛЕЙКОЦИТОВ

Описаны производные 2,6-диаминопурин-β-D-рибофурануронамида, отвечающие формуле I, а также соли указанных соединений, в которых R1 представляет С1-3 -алкильную группу; R2 обозначает С3-C8-циклоалкильную группу, радикалы Alk1Y, -(СНR5)m(Аlk2)nZ, либо замещенную C3-8 -циклоалкильную, пирролидин-3-ильную, 2-оксопирролидин-4-ильную, пиперидин-3-ильную или пиперидин-4-ильную группу; Q является атомом кислорода. Соединения, отвечающие формуле I, а также их соли могут использоваться в медицине в качестве противовоспалительных агентов, особенно при лечении больных, страдающих воспалительными заболеваниями и склонных к вызванному лейкоцитами поражению ткани. 6 с. и 11 з.п. ф-лы, 5 табл.

СПОСОБ ОПРЕДЕЛЕНИЯ ГОМОЦИСТЕИНА В ПРОБЕ И НАБОР ДЛЯ ЕГО ОСУЩЕСТВЛЕНИЯ

Способ предназначен для определения гомоцистеина в пробе и может быть использован для диагностики и лечения в медицине и биотехнологии. Пробу контактируют с ферментом S-аденозилгомоцистеингидролазой ( SAH-аза) в присутствии субстрата, отличного от гомоцистеина. После завершения ферментативной реакции аналит оценивают без хроматографического разделения продуктов реакции. В качестве аналита используют немеченный аналит, выбранный из аденозина, аналога аденозина и S-аденозилгомоцистеина. Способ не требует использования дорогостоящего и трудоемкого хроматографического разделения и позволяет проводить определение в клинической лаборатории. 2 с. и 38 з.п. ф-лы.

АНАЛОГИ ПРИРОДНЫХ ДЕЗОКСИРИБОНУКЛЕОЗИДТРИФОСФАТОВ И РИБОНУКЛЕОЗИДТРИФОСФАТОВ, СОДЕРЖАЩИЕ РЕПОРТЁРНЫЕ ФЛУОРЕСЦЕНТНЫЕ ГРУППЫ, ДЛЯ ИСПОЛЬЗОВАНИЯ В АНАЛИТИЧЕСКОЙ БИООРГАНИЧЕСКОЙ ХИМИИ

Настоящее изобретение относится к аналитической биоорганической химии. Предложенные флуоресцентно-меченные дезоксирибонуклеозидтрифосфаты и рибонуклеозидтрифосфаты имеют общую формулу H-Л-Ф, где Н - модифицированный по конечному атому фосфора природный дезоксирибонуклеозидтрифосфат или рибонуклеозидтрифосфат, Л - линкерная группа, присоединенная к конечному атому фосфора и построенная на основе вторичных диаминов, Ф - репортерная флуоресцентная группа, присоединенная к линкеру посредством вторичной аминогруппы. При этом способ синтеза флуоресцентно-меченных нуклеотидов включает присоединение линкера к флуорофору, активацию трифосфатных групп путем превращения их в циклическую ангидридную форму, взаимодействие активированных трифосфатов с красителями, содержащими линкерную группу, и очистку целевых соединений. Предложенные флуоресцентно-меченные нуклеотиды могут быть использованы в методах одномолекулярного секвенирования, расширяя диапазон возможных условий его проведения. 3 з.п. ф-лы, ...

СПОСОБ ХИМИЧЕСКОГО СИНТЕЗА S-АДЕНОЗИЛ-L-МЕТИОНИНАС ОБОГАЩЕНИЕМ (S, S)-ИЗОМЕРОМ

... 1. Стерео-селективный способ получения S-аденозил-L-метионина (SAMe) формулы (I), или его фармацевтически приемлемых солей: который включает реакцию S-аденозил-L-гомоцистеина (SAH) формулы (II), или его солей с метилирующим агентом формулы (III), где R и R1 могут быть одинаковыми или разными и каждый из которых, независимо друг от друга, является линейным или разветвленным алкильным радикалом, имеющим от 2 до 8 атомов углерода или которые вместе с атомом О, к которому они присоединены, образуют 3-8-членное насыщенное кольцо, которое дополнительно может содержать гетероатомы, выбранные из группы, состоящей из О или S; в присутствии или в отсутствие кислоты. 2. Способ по п.1, в котором соединение формулы (III), выбирают из тетрафторбората 1-метилдиоксания, тетрафторбората 1-метилтетрагидрофурания, тетрафторбората 1-метилтетрагидро-2Н-пирания, тетрафторбората 1-метилоксирания, тетрафторбората 1-метилоксетания или их смеси. 3. Способ по п.1, в котором используемую кислоту выбирают из алифатической ...

НАНОЧАСТИЦЫ НА ОСНОВЕ КОРДИЦЕПИНА/O-КАРБОКСИМЕТИЛХИТОЗАНА И СПОСОБ ИХ ПОЛУЧЕНИЯ

Настоящее изобретение относится к наночастицам на основе кордицепина/О-карбоксиметилхитозана, пригодным для использования в медицине, и способу их получения. Предложены наночастицы на основе кордицепина/О-карбоксиметилхитозана размером 100-200 нм, полученные способом, который включает диспергирование кордицепина в растворе на основе хлорида натрия, содержащем О-карбоксиметилхитозан, добавление к полученной системе раствора триполифосфата натрия, центрифугирование, промывание и вакуумное высушивание. Предложены новые наночастицы, эффективные в качестве носителя кордицепина с замедленным высвобождением и эффективный способ их получения. 2 н. и 8 з.п. ф-лы, 4 пр.

СПОСОБ ОПРЕДЕЛЕНИЯ ГОМОЦИСТЕИНА В ПРОБЕ И НАБОР ДЛЯ ЕГО ОСУЩЕСТВЛЕНИЯ

Предлагается способ определения гомоцистеина в пробе, например, крови, плазмы или мочи, предусматривающий стадии контактирования пробы с превращающим гомоцистеин-ферментом и по меньшей мере одним субстратом для этого фермента, иным, чем гомоцистеин, и оценку без хроматографического разделения немеченого аналита, выбранного из ко-субстрата гомоцистеина и продуктов превращения гомоцистеина упомянутым ферментом. Также предложен набор для осуществления способа.

ХИМЕРНЫЕ РЕЦЕПТОРЫ АНТИГЕНА, НАЦЕЛЕННЫЕ НА PSCA

НОВЫЕ ПРОИЗВОДНЫЕ АДЕНОЗИНА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ НА ИХ ОСНОВЕ, СПОСОБЫ ПОЛУЧЕНИЯ ФАРМАЦЕВТИЧЕСКИХ КОМПОЗИЦИЙ И ИХ ПРИМЕНЕНИЕ

Изобретение относится к производным формулыи их солей прибавления, а также к их применению в терапии, особенно в качестве анальгетических и антигипертензивных препаратов.

ИНГИБИТОРЫ RAS И ИХ ПРИМЕНЕНИЕ

НУКЛЕОЗИДФОСФОРАМИДАТЫ В КАЧЕСТВЕ ПРОТИВОВИРУСНЫХ АГЕНТОВ

ПУРИНМОНОФОСФАТНЫЕ ПРОЛЕКАРСТВА ДЛЯ ЛЕЧЕНИЯ ВИРУСНЫХ ИНФЕКЦИЙ

... 1. Соединение формулы (A) или формулы (B):,или его фармацевтически приемлемая соль или пролекарство, гдеесли хиральность на фосфорном центре существует, она может быть полностью или частично Rили S, или какой-либо их смесью,Rпредставляет собой OH или F;Rи R, при введении in vivo, способны обеспечивать нуклеозидмонофосфат или тиомонофосфат, который либо частично, либо полностью устойчив к 6-NHдезаминированию в биологической системе,Rвыбран из H, Li, Na, K, фенила и пиридинила; фенил и пиридинил являются замещенными одним - тремя заместителями, независимо выбранными из группы, состоящей из (CH)CORи (CH)CON(R);Rнезависимо представляет собой H, Cалкил, углеродную цепь, полученную из жирного спирта, или Cалкил, замещенный низшим алкилом, алкокси, ди(низший алкил)-амино, фтор, Cциклоалкил, циклоалкилалкил, циклогетероалкил, арил, гетероарил, замещенный арил или замещенный гетероарил; где заместители представляют собой Cалкил или Cалкил, замещенный низшим алкилом, алкокси, ди(низшим алкилом)-амино ...

ВАРИАНТЫ ОСУЩЕСТВЛЕНИЯ ЗОНДА И СПОСОБЫ НАПРАВЛЕННОГО ДЕЙСТВИЯ НА НУКЛЕИНОВЫЕ КИСЛОТЫ

... 1. Двухцепочечный зонд, включающийпару мономеров, включающую первый мономер, имеющий формулугде каждый Y независимо выбран из углерода, кислорода, серы, триазола, оксазола, тетразола, изоксазола и NR, где Rвыбран из водорода, алифатического соединения, арила, гетероалифатического соединения и гетероарила; Rи Rвыбраны из водорода, алифатического соединения, арила, алифатического арила и части, содержащей гетероатом; или Rвыбран из функциональной группы, содержащей гетероатом; Rпредставляет собой функциональную группу, содержащую гетероатом; Rвыбран из любого природного или неприродного нуклеинового основания; Rвыбран из интеркалятора, подходящего для интеркаляции в нуклеиновую кислоту; "необязательный линкер" выбран из линкеров, включающих алкильные линкеры, амидные линкеры, карбаматные линкеры, карбонатные линкеры, мочевинные линкеры и их сочетания;второй мономер, имеющий формулугде Y, R, R, R, R, Rи "необязательный линкер" представляют собой указанное для первого мономера; V выбран из ...

СОЕДИНЕНИЕ, СПОСОБ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ ДЛЯ МОДУЛИРОВАНИЯ ЭКСПРЕСИИ DUX4

Предложенная группа изобретений относится к области биотехнологии и может быть использована в медицине. Раскрываются модифицированные олигонуклеотиды, способные к ингибированию экспрессии гена двойного гомеобокса 4 (DUX4). Изобретение может быть применимо при лечении заболеваний, связанных аномальной экспрессий указанного гена у индивидуума, в частности при антисмысловой генной терапии фациоскапуло-плечевой мышечной дистрофии (FSHD), В-клеточного острого лимфоцитарного лейкоза, дифференцированной круглоклеточной саркомы и рабдомиосаркомы плода.10 н. и 19 з.п. ф-лы, 6 ил., 5 табл., 12 пр.

Способ получения (6)-аралкиладенозина

Способ получения сложных эфиров аденозин-5'-карбоновой кислоты

Способ получения комплексных соединений инозина

Способ получения цис-трансизомеров N-(6)-(3-хлорбутен-(2)-ил)-аденозина

DNS-SEQUENZBESTIMMUNG DURCH MASSENSPEKTROMETRIE AUF DEM WEG DES ABBAUS MIT EXONUKLEASE

IN DER HAUPTKETTE MODIFIZIERTE OLIGONUKLEOTID-ANALOGE

Verfahren zur Herstellung von 2-fluor-9-(2,3,5-tri-O-benzyl-beta-arabinofuranosyl)adenin

INDUKTION VON PHARMAKOLOGISCHEM STRESS MIT ADENOSIN-REZEPTOR AGONISTEN

Amphiphile Glycerylnucleotide, Verfahren zu ihrer Herstellung und ihre Verwendung

The invention relates to glyceryl nucleotides of formula (Ia), wherein a) one of the radicals A<1>, A<2> and A<3> represents a hydrogen atom, or a radical selected among hydroxyl, mecapto, alkyl, alkenyl, polyoxyalkenyl, aryl, acyl, alkyloxy, alkenyloxy, polyoxyalkenyloxy, acyloxy, aryloxy, alkylthio, alkenylthio, acylthio or arylthio, whereby the alkyl, alkenyl and acyl radicals are optionally substituted with 1 to 3 aryl radicals; and b1) two of the remaining radicals A<1>, A<2> and A<3> represent two nucleoside groups which are different from one another; or b2) one of the remaining radicals A<1>, A<2> and A<3> represents a nucleoside group and the other of the remaining radicals represents a hydroxycarbonyl group, whereby at least one of the nucleoside groups is not a naturally occurring nucleoside group. The invention also relates to a method for producing these compounds, to pharmaceutical agents containing these compounds, and to the use of these compounds for treating cancer and ...

NUKLEOSID-DERIVATE UND IHRE VERWENDUNG IN DER OLIGONUKLEOSID-SYNTHESE.

OLIGOPYRIDINLIGANDEN, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS KOMPLEXBILDNERMITTEL.

Verfahren zur Herstellung von N-Glykosiden

PROPARGYLPHENYL-ÄTHER A2A REZEPTORAGONISTEN

GRISEOLINSAEUREDERIVATE, IHRE HERSTELLUNG UND IHRE VERWENDUNG.

0,0'-Dicyanoethyl-phosphoramidite, Verfahren zu deren Herstellung und ihre Verwendung in Phosphorylierungsreaktionen.

ALS THERAPEUTISCHE MITTEL VERWENDBARE SUBSTITUIERTE ADENINDERIVATE.

VERFAHREN ZUR HERSTELLUNG VON 2-AMINO-9-(2,3,5-TRI-0-BENZYL-BETA-D-ARABINOFURANOSYL)ADENIN UND NEUE ZWISCHENPRODUKTE

2'-MODIFIZIERTE NUKLEOTIDE

Verfahren zur Herstellung von Purin-Nukleotid-Derivate-dinatrium-Kristallen und Verfahren zur Beseitigung von Alkohol

Verfahren zur Herstellung von Estern der Pyrophosphorsaeure

HETEROZYKLISCHE VERBINDUNGEN

Antivirale Verbindungen

N-6-thienyl-substituierte Adenosinderivate als herzgefässerweiternde Mittel.

Verfahren zur Herstellung von Adenosin-Ketalen

N (6)-alkyladenosines

Adenosines of formula (I):- where R1 is 1-6C alkyl, and R2 is Me or (if R1 Me) H, effect the heart and circulating systems, and influence lipid transfer. Cpds. (I) may be prepd. by reaction of the corresponding 6-halor or mercapto-purineriboside with an amine of formula R1R2 MeCNH2, with appropriate protection of th OH gps.

ADENOSIN-DERIVATE

Verfahren für die Aufreinigung von S-Adenosyl-L-methionin und für die Herstellung von pharmazeutisch annehmbaren Salzen davon

2,6-DIAMINONEBULARINE UND VERFAHREN ZU DEREN HERSTELLUNG

PHARMAZEUTISCHE KOMBINATION VON ADENOSINE A-2A UND BETA-2-ADRENERGEN REZEPTOREN AGONISTEN

S-(+)-Adenosylmethionine und 3'-Azido-2',3'-Dideoxy-Nukleosid-Komplexe als potente Inhibitoren von HIV-Replikation

C2,8-disubstituted adenosine derivatives and their different uses

Bioreductively-activated prodrugs

Chemical compounds

N-6- SUBSTITUTED ADENOSINE DERIVATIVES

... 1340643 N(6)-substituted adenosine derivatives BOEHRINGER MANNHEIM GmbH 18 July 1972 [22 July 1971] 33573/72 Heading C2C Novel compounds I in which R 1 is H, halo, NH 2 or OH; R 2 is NO 2 , CN, or CH 2 OH and R 3 is H, halo, alkyl or alkoxy and salts thereof are prepared by reaction of a compound II in which X is halo or a reactive mercapto grouping with a compound III or where R 1 is H by heating a compound IV in alkaline solution. Pharmaceutical compositions comprise a compound I together with a suitable diluent or' carrier. They are administered orally, rectally or parenterally and have circulatory action.

DOUBLE SALTS OF S -ADENOSYL-L-METHIONINE

... 1443587 Double salts of S-adenosyl-L- methionine BIORESEARCH SaS 24 June 1974 [27 June 1973 24 May 1974] 27888/74 Heading C2C Novel double salts of S-adenosyl-L-methionine (SAM) with sulphuric acid and p-toluenesulphonic acid, especially of the formula are prepared by (a) preparing a concentrated solution of SAM, (b) precipitating the SAM therefrom by addition of a solution of picrolonic acid, (c) dissolving the precipitated SAM picrolonate in a mixture consisting of equal parts by volume of an aqueous solution containing equinormal amounts of p-toluene sulphonic acid and sulphuric acid and of an organic solvent at least partially miscible with water, (d) precipitating the resultant SAM salt from the aqueous layer by addition of a ketone or alcohol based solvent fully miscible with water, (e) dissolving the precipitated salt in a solution of p-toluenesulphonic acid in methanol, and (f) precipitating the double salt of SAM with sulphuric acid and p-toluenesulphonic acid by addition of a ...

PREPARATION OF 5'-DEOXY-5'-METHYL-THIOADENOSINE

ANTIVIRAL COMPOUNDS

Process for the Purification of Reduced Pyridine Coenzymes

... 1,197,415. Purifying pyridine coenzymes. BOEHRINGER MANNHEIM G.m.b.H. 2 Jan., 1969 [20 March, 1968], No. 4467/69. Heading C2C. Nicotinamide - adenine - dinucleotide and nicotinamide - adenine - dinucleotide phosphate are purified by a chromatographic process wherein there is used a weakly basic anion exchange resin which is not present in the hydroxyl form, and the elution is carried out at pH of more than 7À5, preferably 9-12. The column may be loaded with acetate, formate, carbonate or sulphate ions, and specified elution agents are triethyl-ammonium carbonate triethyl ammonium formate, trihydroxymethylaminomethane formate, sodium sulphate, and sodium formate. The elution system preferably contains organic solvents, isopropanol being particularly preferred.

Chemical compounds

2-SUBSTITUTED ADENOSINE DERIVATIVES AND THE PRODUCTION THEREOF

... 1367785 Adenosine derivatives TAKEDA YAKUHIN KOGYO KK 23 Sept 1971 [25 Sept 1970] 44341/71 Heading C2C Novel compounds of Formula I (in which R is a C 2-4 alkyl or phenyl radical and is unsubstituted or substituted by at least one nitro, halogen, alkyl or alkoxy substituent) and their pharmaceutically acceptable salts, are prepared by 5-amino-1-(#-D-ribofuranosyl)-4-imidazole-carbonitrile with a compound of formula R.CN, in the presence of a base, and optionally converting the product into a pharmaceutically acceptable salt. Pharmaceutical compositions having coronary dilatory and hypotensive activity, for oral or parenteral administration comprise one or the above novel compounds together with a pharmaceutical carrier.

3-deoxy-ribofuranosyl derivatives

Compounds of the formula where X is halogen and R is an acyl radical may be obtained by reacting a compound of the formula wherein R11 is an alkyl group, with a halogenating system capable of producing a halogen anion in the presence of a strong acid under anhydrous conditions, suitably in the presence of an inert organic solvent. The halogenating agent may be a hydrogen or thionyl halide (both of which may also function as the strong acid) or a metal halide.

NOVEL ENTITIES FOR CANCER THERAPY

Adenosine derivatives of anti-inflammatory and analgesic activity and therapeutic compositions containing them

A therapeutic composition of antiinflammatory, analgesic and antipyretic activity comprises as its active principle, at least one component of the general formula: in which R is a linear or branched alkyl radical containing 1-18 C atoms or a phenylalkylene in which the alkylene chain contains 1-6 C atoms; R1 is H, an aliphatic acyl radical containing 1-6 C atoms or an aromatic acyl radical; R2 is an aliphatic acyl radical containing 1-6 C atoms, or an aromatic acyl radical, or the radicals R2 together form an isopropylidene chain; and n is 0 or 1, or an acid additive salt of a compound of formula (I) in which R' is hydrogen.

ADENOSINE DERIVATIVES OF ANTI-INFLAMMATORY AND ANALGESIC ACTIVITY AND THERAPEUTIC COMPOSITIONS CONTAINING THEM

Alkyl ether congeners of hexitol nucleoside analogues (HNA)

Modified nucleotides

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3'-OH blocking group covalently attached thereto, such that the 3' carbon atom has attached a group of the structure -O-Z wherein Z is any of -C(R')2-O-R'', -C(R')2-N(R'')2,-C(R')2-N(H)R'', -C(R')2-S-R'' and -C(R')2-F, wherein each R'' is or is part of a removable protecting group; each R' is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R')2 represents an alkylidene group of formula =C(R''')2 wherein each R''' may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R'' is exchanged for H or, where ...

Preparation of inosine

In the preparation of inosine by deamination of adenosine with nitrous acid, the nitrous acid is formed in situ from an inorganic or organic nitrite, the pH is at least 1.5, preferably 1.9 to 4.0, and an excess of nitrous acid is used, e.g. 10 to 20 mols of nitrous acid per mol of adenosine. Barium nitrite may be used, in which case it is reacted with sulphuric acid and the precipitate removed, or ethyl nitrite may be used. Nitric acid is formed as the deamination proceeds, and is neutralized to maintain the pH above 1:5, or it is removed by an anion exchanger. The inosine may be separated by crystallization, or precipitated with a metal salt, e.g. a silver salt from which it is recovered by reaction with a sulphide. In examples ethyl nitrite is reacted with aqueous suspension of adenosine.

Purine derivatives and their preparation

The invention comprises 2-amino-6-chloro-9-21,31, 51-tri-O-acylb -D-ribofuranosylpurines and the preparation thereof and of 6-chloro-9-21,31, 51- tri-O-acyl-b -D- ribofuranosylpurine by treating 21,31,51-tri-O-acylguanosines or 21,31,51-tri-O-acylinosines with a chlorinating agent, e.g. phosphoryl chloride. 21,31,51-Tri-O-acetyl- and -benzoyl-guanosine and -inosine are prepared by treating guanosine or inosine with acetic anhydride or benzoyl chloride, in the presence of pyridine. 6-Mercapto- and 2-amino-6-mercapto-9-b -D-ribofuranosylpurines are prepared from the corresponding 6-chloro-tri-O-acyl compounds by thiation followed by deacylation.

A process for the preparation of 2,3-o-isopropylidene purine ribonucleosides

In a process for the production of 21, 31-O-isopropylidene purine ribonucleosides, a purine nucleoside is reacted with acetone in the presence of a solution of an inorganic acid or an organic sulphonic acid in an alcohol, a phenol or an ethylene glycol ether or ester.

Therapeutic compounds

A fermentation process for the production of purine derivatives

Purine derivatives of the general formula in which R represents -H, or where n is 1, 2 or 3, X represents = O, -H -OH, or -NH2, and Y represents = O, -OH, or -NH2, but not -NH2 when X is -OH or -NH2, there being one or two further double bonds and one or two hydrogen atoms on the ring nitrogen atoms in the 6-membered ring if there is one or no = O group respectively as a substituent in the 6-membered ring, are prepared by inoculating a microbial mutant, which is resistant to an antimetabolite in purine metabolism, into a culture medium containing an assimilable carbon source and a utilizable nitrogen source, incubating the culture until the purine derivatives are accumulated in the culture broth, and recovering these derivatives from the broth. Original micro-organisms from which the desired mutants can be induced are those strains whose growth is inhibited by the presence of an antimetabolite in purine metabolism, which strains ...

ISOMERIC O-PHOSPHONYLMETHYL DERIVATIVES

ENHANCER OF ANTI-TUMOR EFFECT

THERAPEUTIC NUCLEOSIDES

ANTI-VIRAL COMPOUNDS

Purine derivatives

... 1,133,835. Nucleosides. MERCK & CO. Inc. 24 Jan., 1966 [29 Jan., 1965], No. 3110/66. Heading C2C. The invention comprises (1) compounds of formulµ where R is a hydrogen, chlorine or bromine atom or an amino, alkylamino dialkylamino, hydroxy or mercapto group, R is a hydrogen atom or an amino group, provided that R 1 is not hydrogen when R is amino, X is a hydrogen, chlorine or bromine atom, a mercapto or hydroxy group or a group -NR 3 Y wherein Y is an acyl residue derived from an organic carboxylic acid and R 3 is hydrogen or alkyl, Z is hydrogen or a group -NHY, and R 2 is an acyl group derived from an organic carboxylic acid, and (2) 7-(3-deoxy-#-D)-ribofuranosyl) and its 2-acetyl-21,51-dibenzoyl derivative, and their preparation by reaction of a diacylated 3- deoxy - ribofuranosyl 1 - halide with the mercury halide salt of a substituted purine, followed if desired by one or more of (a) hydrolysis of acylamino and/or ester groups; (b) reaction of a halo-substituted ...

Molecular Compound of Inosine-Tryptophan

... 1,180,635. Molecular compound of inosinetryptophan. AJINOMOTO CO. Inc. 19 June, 1967 [18 June, 1966; 28 Jan., 1967], No. 28248/67. Heading C2C. A novel molecular compound of optically active tryptophan and inosine comprising equimolar amounts of each is prepared by (a) mixing an aqueous solution of inosine with an aqueous solution of tryptophan; (b) adding solid tryptophan to an aqueous solution of inosine; (c) adding solid inosine to an aqueous solution of tryptophan; or (d) reacting the two components under suspension or slurry conditions. As starting materials free inosine and its salts, e.g. alkali metal salts, may be used together in the free tryptophan or a salt thereof, e.g. the hydrochloride. By virtue of their different solubilities the molecular compounds of D-tryptophan and L-tryptophan with inosine may be separated by fractional crystallization. The molecular compound is split into its two components by ion-exchange chromatography or by contact with methanol in which only the ...

N6-3-CHLOROBUTEN-2-YL-ADENOSINES AND PROCESSES FOR THEIR MANUFACTURE

... 1338421 Adenosines SCHERING AG 14 Dec 1970 [12 Dec 1969] 59309/70 Heading C2C [Also in Division A5] cis- and trans - N6 - [3 - Chlorobuten - (2) - yl] adenosine are prepared by (a) reacting 6-chloronebularin with 3-chlorobuten-(2)-ylamine in the presence of a base, (b) reacting adenosine with 1,3-dichlorobutene-(2) in the presence of a base or (c) reacting adenosine with 1,3 - dichlorobutene-(2) in the absence of a base and treating the product with a base.

ARABINOFURANOSYL PURINES AND PYRIMIDINES

... 1,211,808. Arabinofuranosyl purines and pyrimidines. MERCK & CO. Inc. 5 Aug., 1968 [8 Aug., 1967], No. 37293/68. Heading C2C. Novel compounds A in which R is H, benzyl or substituted benzyl; R1 is amino or phthalimido and Z is of Formula B or C in which J and K are H, halo, OH, SH, alkylthio, NH 2 , benzylamino, mono- or di-alkylamino, alkenylamino, or benzylmercapto; L is alkoxy, OH, NH 2 , mono- or di-alkylamino; and M is H, halo, alkyl, haloalkyl, SH, alkylthio, aralkylthio, NH 2 , mono- or di-alkylamino are prepared by reacting a compound VIII in which R‹ is benzyl or substituted benzyl with the appropriate purine or pyrimidine compounds, followed, where desired, by conversion of the phthalimido group to amino using hydrazine hydrate and/or reduction of the R‹ groups to, H. In any compound A the groups J, K, L and M can be modified by conventional methods to give other groups J, K, L and M. Intermediates isolated are methyl D-arabinofuranoside, prepared by reaction of methanol ...

Purine derivatives

ANTIBIOTICS

Purine derivatives

Antiviral nucleoside analogues

Chemical compounds

methods and compositions for treating hepatitis C virus

Phosphonate analogs of HIV inhibitor compounds

Adenosine derivatives

2-(Purin-9-yl)-tetrahydrofuran-3,4-diol derivatives

Substituted nucleosides, nucleotides and analogs thereof

Compounds having antih perte sive cardioprotective anti-ischemic and antilopolytic properties

Compounds having antihypertensive cardioprotective anti-ischemic and antilipolytic properties

Chemical compounds

Adenosine derivatives and analogues which posses adenosine agonist activity.

This invention relates to adenosine derivatives of the following general formula: and analogs which possess adenosine agonist activity and are useful as anti-hypertensive, cardioprotective, anti-ischemic, and antilipolytic agents, to pharmaceutical compositions including such compounds, and to their use in treating hypertension, myocardial ischemia, ameliorating ischemic injury and myocardial infarct size consequent to myocardial ischemia, and treating hyperlipidemia and hypercholesterolemia, and to methods and intermediates used in the preparations of such compounds.

Therapeutic nucleosides

This invention ...

2,6-Diaminopurine derivatives.

... 2,6-Diaminopurine- ...

Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties.

This invention relates to adenosine derivatives and analogues which possess biological activity and are useful as anti-hypertensive, cardioprotective, anti-ischemic. and antilipolytic agents, to pharmaceutical compositions.including such compounds, and to their use in treating hypertension, myocardial ischemia, ameliorating ischemic injury and myocardial infarct size consequent to myocardial ischemia, and treating hyperlipidemia and hypercholesterolemia, and to methods and intermediates used in the preparation of such compounds.

Purine derivatives

The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, to process for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as adenosine A2a receptor agonists.

Purine derivatives

Purine derivatives.

The present invention relates to compounds of the formula and pharmaceutically acceptable salts and solvates thereof, to processes for the preparation of, intermediates used in the preparation of, and compositions containing such compounds and the uses of such compounds as adenosine a2a receptor agonists.

Preparation of 2-chloro-9-(2'-deoxy-2'-fluoro-Beta-D-arabinofuranosyl)-adenine

A process for making clofarabine comprising: fluorinating a compound of formula VII wherein each R 4 is independently a hydroxy protecting group, OR 6 is a leaving group, with a fluorinating agent in the presence of guanidine carbonate to give a compound of formula VIII: wherein R 4 is as defined above; and deprotecting the compound of formula VIII to give the clofarabine.

Labelling Strategies for the Sensitive Detection of Analytes

The present invention relates to methods and reagents for detecting analytes, e.g. nucleic acids. The new methods and reagents allow a simple and sensitive detection even in complex biological samples.

Phosphonate nucleosides useful as active ingredients in pharmaceutical compositions for the treatment of viral infections, and intermediates for their production

Disclosed herein are novel phosphonate nucleosides and thiophosphonate nucleosides comprising a phosphonalkoxy-substituted or phosphonothioalkyl-substituted five-membered, saturated or unsaturated, oxygen-containing or sulfur-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

2'-fluoro arabino nucleosides and use thereof

A method of treating cancer using certain 2′-fluoro arabino nucleosides is provided. Also provided are compounds represented by the formula: (I & A) wherein R is alkyl; and pharmaceutically acceptable salts thereof; and pharmaceutical compositions containing these compounds.

Methods for transdifferentiation of body tissues

The invention relates to methods for transdifferentiation of body tissues which can be used to generate specific cell types needed for regenerating organs or body parts, following cellular degeneration, injury or amputation. The present invention also describes the use of tissue transdifferentiation for treating cancer and autoimmune disease.

Bridged artificial nucleoside and nucleotide

It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2′,4′-BNA/LNA. The oligonucleotide containing the 2′,4′-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2′,4′-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity

Compounds and pharmaceutical compositions for the treatment of viral infections

Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Novel nucleic acid prodrugs and methods of use thereof

Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

Synthesis of purine nucleosides

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

Methods and compositions for treating hepatitis c virus

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Compounds, Compositions and Methods of Using Same for Modulating Uric Acid Levels

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

N6-substituted adenosine derivatives and n6-substituted adenine derivatives and uses thereof

The present invention provides N 6 -substituted adenosine derivatives and N 6 -substituted adenine derivatives, manufacturing methods thereof, a pharmaceutical composition comprising the said compounds above, and uses of these compounds in manufacturing medicaments and health-care products for treating insomnia, convulsion, epilepsy, and Parkinson's diseases, and preventing and treating dementia.

2'-CHLOROACETYLENYL SUBSTITUTED NUCLEOSIDE DERIVATIVES

The present invention relates to 2′-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): 9. A pharmaceutical composition comprising an inhibitory amount of a compound according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.10. A method of treating a viral infection in a subject claim 9 , comprising administering to the subject an inhibitory amount of a pharmaceutical composition according to .11. The method according to claim 10 , wherein the viral infection is hepatitis C virus.12. A method of inhibiting the replication of hepatitis C virus claim 9 , the method comprising supplying a hepatitis C viral NS3 protease inhibitory amount of the pharmaceutical composition of .13. The method of further comprising administering concurrently an additional anti-hepatitis C virus agent.14. The method of claim 11 , wherein said additional anti-hepatitis C virus agent is selected from the group consisting of α-interferon claim 11 , β-interferon claim 11 , ribavarin claim 11 , and adamantine.15. The method of claim 12 , wherein said additional anti-hepatitis C virus agent is an inhibitor of hepatitis C virus helicase claim 12 , polymerase claim 12 , metalloprotease claim 12 , or IRES.16. The pharmaceutical composition of claim 9 , further comprising another anti-HCV agent.17. The pharmaceutical composition of claim 9 , further comprising an agent selected from interferon claim 9 , ribavirin claim 9 , amantadine claim 9 , another HCV protease inhibitor claim 9 , an HCV polymerase inhibitor claim 9 , an HCV helicase inhibitor claim 9 , or an internal ribosome entry site inhibitor.18. The pharmaceutical composition of claim 9 , further comprising pegylated interferon.19. The pharmaceutical composition of claim 9 , further comprising another anti-viral claim 9 , anti-bacterial claim 9 , anti-fungal or anti-cancer agent claim 9 , or an immune modulator.20. The composition of claim 9 , further comprising a cytochrome P450 ...

Phosphonate analogs of hiv inhibitor compounds

The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

CRYSTALLIZATION PROCESS OF CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE

Provided is a crystallization process of cyclic adenosine 3′,5′-monophosphate, which comprises the following steps: 1) reacting an aqueous solution of cyclic adenosine 3′,5′-monophosphate with a base to obtain a salt of cyclic adenosine 3′,5′-monophosphate; 2) reacting the cyclic adenosine 3′,5′-monophosphate salt solution obtained in step 1) with an acid to obtain cyclic adenosine 3′,5′-monophosphate; 3) keeping cyclic adenosine 3′,5′-monophosphate obtained in step 2) at 0-15° C. 110-. (canceled)11. A crystallization method of 3′ ,5′-cyclic adenosine monophosphate , wherein said method comprises the following steps:1) reacting 3′,5′-cyclic adenosine monophosphate aqueous solution with a base to produce 3′,5′-cyclic adenosine monophosphate salt solution;2) reacting the 3′,5′-cyclic adenosine monophosphate salt solution produced in step 1) with an acid to produce 3′,5′-cyclic adenosine monophosphate; and3) preserving the 3′,5′-cyclic adenosine monophosphate produced in step 2) at 0-15° C.12. The method according to claim 11 , wherein in said step 1) claim 11 , 3′ claim 11 ,5′-cyclic adenosine monophosphate aqueous solution is reacted with a base until the pH value of the solution reaches pH 6.0-10.0.13. The method according to claim 12 , wherein said base is one or more selected from ammonia water and sodium hydroxide claim 12 , the concentration of which is 2-10 M.14. The method according to claim 12 , wherein the concentration of said 3′ claim 12 ,5′-cyclic adenosine monophosphate aqueous solution is 15-350 g/L.15. The method according to claim 11 , wherein in said step 2) claim 11 , 3′ claim 11 ,5′-cyclic adenosine monophosphate salt solution is reacted with an acid until the pH value of the solution reaches pH 1.0-5.0.16. The method according to claim 15 , wherein said acid is one or more selected from sulfuric acid claim 15 , hydrochloric acid and phosphoric acid claim 15 , the concentration of which is 0.01-10 M.17. The method according to claim 11 , wherein ...

Method of ameliorating oxidative stress and supplementing the diet

A method of supplementing a diet and ameliorating oxidative stress in a mammal includes administering a pharmaceutically effective amount of lipid soluble, hydrophobic active compounds having a chemical structure: wherein R 1 is an aromatic backbone and R 2 is a sulfur containing ligand. Through formation of disulfide linkages other moieties can be attached to R 2 converting the hydrophobic base into a water soluble entity, for ease of delivery, which can be reconverted back to the original compound by biochemical reduction in the blood stream.

AGENT FOR ENHANCING THE EFFECT OF SKIN-WHITENING INGREDIENTS AND USES THEREOF

The present invention has objects to provide an agent for enhancing the effect of skin-whitening ingredients which enhances the skin-whitening action of skin-whitening ingredients and has an improved safeness, and to provide a skin-whitening agent, which contains the above agent and a skin-whitening ingredient(s) and has an improved and enhanced skin-whitening action. The present invention solves the above objects by providing an agent for enhancing the effect of skin-whitening ingredients, which contains one or more members selected from the group consisting of guanine and derivatives thereof as an effective ingredient(s); and a skin-whitening agent which contains the above agent along with a skin-whitening ingredient(s) particularly, members derivatives thereof and/or equol including derivatives thereof. 1. An agent for enhancing the effect of skin-whitening ingredients , which comprises one or more members selected from the group consisting of guanine including derivatives thereof as an effective ingredient(s).2. The agent of claim 1 , wherein said guanine including derivatives thereof is one or more members selected from the group consisting of guanine claim 1 , guanosine claim 1 , guanosine monophosphate claim 1 , guanosine diphosphate claim 1 , guanosine triphosphate claim 1 , and glucosylguanosine.3. The agent of claim 1 , which enhances the skin-whitening action of adenine including derivatives thereof and/or equol including derivatives thereof.4. The agent of claim 3 , wherein said adenine including derivatives thereof is one or more members selected from the group consisting of adenine claim 3 , adenosine claim 3 , adenosine monophosphate claim 3 , adenosine diphosphate claim 3 , adenosine triphosphate claim 3 , and glucosyladenosine.5. The agent of claim 3 , wherein said equol including derivatives thereof is equol and/or glycosylequol.6. A skin-whitening agent claim 1 , which comprises the agent of and adenine including derivatives thereof claim 1 , ...

Crystal Forms of 2--Adenosine

The present invention provides novel crystalline polymorphic forms of 2-cyclohexylmethylidenehydrazino adenosine, also known as binodenoson, methods of making the same, and methods for the manufacture of a pharmaceutical composition by employing such crystal forms, in particular, for the use of binodenoson in a subject, in need thereof, as a pharmacological stress agent to produce coronary vasodilation. 1. A crystal form of 2-{2-[(cyclohexyl)methylene]hydrazino}adenosine (binodenoson) which crystal form is substantially free of other polymorphic forms of binodenoson and has at least one of the following properties:(a) an endotherm by differential scanning calorimetry with an extrapolated onset melting temperature in the range of about 139° C. to about 146° C. when heated at 10° C./min;(b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 5.7±0.2, 10.2±0.2, 14.6±0.2, 19.9±0.2, 21.1±0.2 and 24.6±0.2;(c) an infrared reflectance spectrum with reflectance bands at about 1668±2 and 1592±2; and{'sup': '−1', '(d) a Raman spectrum with Raman shifts at about 1618±2 and 1593±2 cm.'}3. A crystal form according to claim 1 , which crystal form has all four of the properties (a) claim 1 , (b) claim 1 , (c) and (d).4. A crystal form of binodenoson which crystal form is substantially free of other polymorphic forms of binodenoson and has at least one of the following properties:(a) an endotherm by differential scanning calorimetry with an extrapolated onset melting temperature in the range of about 149° C. to about 154° C. when heated at 10° C./min;(b) a X-ray diffraction pattern with characteristic X-ray diffraction peaks at diffraction angles (2θ) of about 5.5±0.2, 10.4±0.2, 16.8±0.2, 20.2±0.2 and 26.0±0.2;{'sup': '−1', '(c) an infrared reflectance spectrum with reflectance bands at about 1646±2 and 1598±2 cm; and'}{'sup': '−1', '(d) a Raman spectrum with Raman shifts at about 1622±2 and 1588±2 cm.'}6. A crystal form ...

PROCESS FOR THE SYNTHESIS OF CARBONUCLEOSIDE AND INTERMEDIATES FOR USE THEREIN

Disclosed is a process for preparing a carbonucleoside of formula (1) and intermediates for use therein. The process involves the step of reacting a compound of formula (2) with a compound of formula (3) under Mitsunobu-type reaction conditions to obtain a compound of formula (4), wherein PG, PG, PGand PGare protecting groups. The compound of formula (4) is deprotected to form the compound of formula (1), as shown below. 2. The process according to claim 1 , wherein the Mitsunobu type reaction condition comprises an alkyl phosphine or an aryl phosphine claim 1 , and an azo-based compound.3. The process according to claim 2 , wherein the alkyl phosphine is PMe.4. The process according to claim 2 , wherein the aryl phosphine is PPh.5. The process according to claim 2 , wherein the azo based compound is selected from the group consisting of diethylazodicarboxylate (DEAD) claim 2 , diisopropylazodicarboxylate (DIAD) claim 2 , di-t-butylazodicarboxylate claim 2 , 2-(phenylazo)pyridine (azpy) claim 2 , di-p-chlorobenzylazodicarboxylate (DCAD) or 1 claim 2 ,1′-(azodicarboxyl)dipiperidine (ADDP).6. The process according to claim 2 , wherein the azo based compound is diisopropylazodicarboxylate (DIAD).7. The process according to claim 1 , wherein the Mitsunobu type reaction condition comprises a phosphorane ylide.8. The process according to claim 7 , wherein the phosphorane ylide is selected from the group consisting of (cyanomethylene)trimethyl phosphorane or tributylphosphorane.9. The process according to claim 1 , wherein solvent for the Mitsunobu type reaction is selected from the group consisting of tetrahydrofuran claim 1 , acetonitrile claim 1 , dichloromethane claim 1 , toluene claim 1 , or a mixture thereof.10. The process according to claim 1 , wherein solvent for the Mitsunobu type reaction is tetrahydrofuran.11. The process according to claim 1 , wherein the Mitsunobu type reaction is carried out at room temperature.12. The process according to claim 1 , wherein ...

METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided. 2. The method of claim 1 , wherein Rand Rare each independently H; phosphate; a stabilized phosphate prodrug; acyl; or a pharmaceutically acceptable leaving group which claim 1 , when administered in vivo claim 1 , provides a compound wherein Rand Rare each independently H or phosphate.3. The method of claim 1 , wherein Ris hydrogen claim 1 , acyl claim 1 , or phosphate.4. The method of claim 1 , wherein Ris hydrogen or phosphate.5. The method of claim 1 , wherein Ris phosphate.6. The method of claim 1 , wherein Ris hydrogen or acyl.7. The method of claim 1 , wherein Ris hydrogen.8. The method of claim 1 , wherein Ris alkyl.9. The method of claim 1 , wherein Ris methyl.10. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —C(O)O(alkyl) claim 1 , —C(O)O(lower alkyl) claim 1 , —O(acyl) claim 1 , —O(lower acyl) claim 1 , —O(alkyl) claim 1 , —O(lower alkyl) claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).11. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).12. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , azido claim 1 , cyano ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof. 3. The compound of claim 1 , wherein Ris an optionally substituted acyl.4. The compound of claim 1 , wherein Ris H.5. The compound of claim 1 , wherein Ris an optionally substituted O-linked amino acid.7. The compound of claim 6 , wherein both Rand Rare independently selected from the group consisting of an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl claim 6 , an optionally substituted Ccycloalkenyl claim 6 , an optionally substituted aryl claim 6 , an optionally substituted heteroaryl and an optionally substituted aryl(Calkyl).10. The compound of claim 6 , wherein Ris selected from the group consisting of absent claim 6 , hydrogen claim 6 , an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl and an optionally substituted Ccycloalkenyl; and Ris independently selected from the group consisting of an optionally substituted Calkyl claim 6 , an optionally substituted Calkenyl claim 6 , an optionally substituted Calkynyl claim 6 , an optionally substituted Ccycloalkyl claim 6 , an optionally substituted Ccycloalkenyl and NRR.11. The compound of claim 6 , wherein Ris an optionally substituted aryl; and Ris an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.12. The compound of claim 6 , wherein Rand Rare both an optionally substituted N-linked amino acid ...

LINKED PURINE PTERIN HPPK INHIBITORS USEFUL AS ANTIBACTERIAL AGENTS

The disclosure provides linked purine pterin compounds and analogues thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I 5. A compound or salt thereof of claim 2 , wherein{'sub': 1', '3', '2, 'Ais oxo and each Ais independently chosen from hydrogen and methyl; and Ris —NH—.'}6. A compound or salt thereof of any one of claim 5 , wherein{'sub': '1', 'Ris methylene optionally substituted with —(C═O)—.'}7. (canceled)8. A compound or salt thereof of claim 2 , wherein{'sub': 1', '1', '1', '4', '1', '4', '1', '2', '1', '2, 'Lis an alkylene linker having from 2 to 4 carbon atoms, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, amino, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy; and'}{'sub': 2', '2', '1', '4', '1', '4', '1', '2', '1', '2', '1', '2, 'Lis an alkylene linker having from 1 to 2 carbon atoms, containing 1 heteroatom selected from oxygen, nitrogen, and sulfur, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, amino, C-Calkyl, C-Calkoxy, C-Chaloalkyl, and C-Chaloalkoxy; wherein the total number of carbon atoms in the Land Lalkylene linkers is from 3 to 5'}9. (canceled)10. A compound or salt thereof of claim 8 , wherein{'sub': 1', '1, 'Lis an alkylene linker having from 2 to 3 carbon atoms, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from halogen and methyl;'}{'sub': 2', '2', '2, 'Lis an alkylene linker of the formula —SCH—, wherein Lis unsubstituted or substituted with 1 or more substituents independently chosen from halogen and methyl; and'}{'sub': 3', '3', '1', '2', '1', '2, 'Ris a piperidinyl, piperazinyl, or pyrrolidinyl ring; each of which Ris unsubstituted or substituted with 1 or more substituents independently chosen from hydroxyl, halogen, C-Calkyl, and C-Calkoxy.'} ...

METHOD FOR OXIDIZING ALCOHOLS

A method for oxidizing an alcohol, wherein oxidation is performed in the presence of a compound represented by the following formula (I) and a bulk oxidant, which enables efficient oxidation of secondary alcohols as well as primary alcohols, and can attain high reaction efficiency even when air is used as a bulk oxidant. 2. The method according to claim 1 , wherein the alcohol is a secondary alcohol.3. The method according to claim 1 , wherein the bulk oxidant is a peracid claim 1 , hydrogen peroxide claim 1 , a hypohalogen acid or a salt thereof claim 1 , a perhalogen acid or a salt thereof claim 1 , a persulfuric acid salt claim 1 , a halogenating agent such as a halide and N-bromosuccinimide claim 1 , a trihalogenated isocyanuric acid claim 1 , a diacetoxyiodoallene claim 1 , a dialkyl azodicarboxylate claim 1 , oxygen claim 1 , air claim 1 , or a mixture thereof.4. The method according to claim 1 , wherein the bulk oxidant is air.5. The method according to claim 2 , wherein the bulk oxidant is a peracid claim 2 , hydrogen peroxide claim 2 , a hypohalogen acid or a salt thereof claim 2 , a perhalogen acid or a salt thereof claim 2 , a persulfuric acid salt claim 2 , a halogenating agent such as a halide and N-bromosuccinimide claim 2 , a trihalogenated isocyanuric acid claim 2 , a diacetoxyiodoallene claim 2 , a dialkyl azodicarboxylate claim 2 , oxygen claim 2 , air claim 2 , or a mixture thereof.6. The method according to claim 2 , wherein the bulk oxidant is air. The present invention relates to a method for oxidizing an alcohol utilizing an organic catalyst.Oxidation reactions of alcohols constitute one class of important reactions as methods for chemical conversion of compounds, and are frequently used in syntheses of organic compounds with high added values such as medicaments and agricultural chemicals and the like. Therefore variety of methods have been developed so far. However, many of those methods use explosive reagents, highly toxic metals and the ...

Anhydrous polymorphs of [(2r,3s,4r,5r)-5-(6-(cyclopentylamino)-9h-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)} methyl nitrate and processes of preparation thereof

The present invention provides novel anhydrous polymorph forms of 2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate (Compound A). The present invention also provides processes for preparation of the anhydrous polymorphic forms of compound A.

COMPOUNDS FOR TREATING BACTERIAL INFECTIONS

Rel proteins as a novel therapeutic agent for treating bacterial threats. More specifically, a novel class of compounds of Formula (I) as disclosed herein which possess anti-bacterial activity and which inhibit RelA, RelSeq or RelSpo synthetic activity or bacterial spore formation. Also, pharmaceutical compositions of such compounds and a method of combating bacteria, or treating bacterial infections, by administering to a subject in need thereof such compounds or pharmaceutical compositions. 143.-. (canceled)47. The compound according to claim 44 , wherein Ris H or —CO—CH(CH).49. The compound according to claim 44 , wherein Rand Rare each independently H or methyl.50. The compound according to claim 44 , wherein Ris independently at each occurrence H claim 44 , methyl claim 44 , ethyl or benzyl.51. The compound according to claim 44 , wherein Ris H or phenyl.63. An anti-bacterial pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 44 , and a pharmaceutically acceptable carrier or excipient.64. A method of combating bacteria claim 44 , or treating bacterial infections claim 44 , comprising the step of administering to a subject in need thereof a compound according to claim 44 , or a pharmaceutical composition comprising such compound. The present invention generally relates to Rel proteins as a novel therapeutic target for treating bacterial threats and more specifically to a novel class of 2′-deoxyguanosine analogs, which possess anti-bacterial activity, to pharmaceutical compositions comprising such compounds, and to methods of use thereof for combating bacteria and treating bacterial infections.Bacteria cells present an outstanding ability to rapidly react to various changes in their growth environment. The number of useful antibiotic agents is decreasing fast. Thus, there is an urgency for finding alternative ways to deal with the crisis.The natural environment of bacteria is often characterized by changes in ...

2' AND 5' MODIFIED MONOMERS AND OLIGONUCLEOTIDES

The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. 10. The oligonucleotide of claim 5 , wherein at least one of Tand Tis methyl.11. The oligonucleotide of claim 5 , wherein one of Tand Tis methyl and the other of T claim 5 , and Tis H.12. The oligonucleotide of wherein Xis O.13. The oligonucleotide of wherein Xis S.14. The oligonucleotide of wherein Xis CHor CF.15. The oligonucleotide of wherein the oligonucleotide comprises:1-20 first-type regions, each first-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each first-type region comprises a first-type modification;0-20 second-type regions, each second-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each second-type region comprises a second-type modification; and0-20 third-type regions, each third-type region independently comprising 1-20 contiguous nucleosides wherein each nucleoside of each third-type region comprises a third-type modification;{'sub': 3', '2', '3, 'wherein the first-type modification, the second-type modification, and the third-type modification are each independently selected from the group consisting of 2′-F, 2′-OCH, 2′-O(CH)2OCH, BNA, F-HNA, 2′-H and 2′-OH.'}16. The oligonucleotide of claim 5 , wherein the oligonucleotide comprises at least one non-phosphodiester internucleoside linkage.17. The oligonucleotide of claim 16 , wherein at least one of the non-phosphodiester internucleoside linkage is selected from the group consisting of phosphorothioate claim 16 , phosphorodithioate claim 16 , alkyl- ...

Methods for the Identification of Methyltransferase Interacting Molecules and for the Purification of Methyltransferase Proteins

The present invention relates to immobilization compounds, immobilization products and preparations thereof as well as methods and uses for the identification of methyltransferase interacting compounds or for the purification or identification of methyltransferase proteins. 3. A method for the preparation of an immobilization product claim 1 , wherein the immobilization compound of is immobilized on a solid support claim 1 , in particular wherein the solid support is selected from the group consisting of agarose claim 1 , modified agarose claim 1 , sepharose beads (e.g. NHS-activated sepharose) claim 1 , latex claim 1 , cellulose claim 1 , and ferro- or ferrimagnetic particles.4. The method of claim 3 , wherein the immobilization product results from a covalent direct or linker mediated attachment of the immobilization compound to the solid support claim 3 , in particular wherein the linker is a Calkylene group claim 3 , which is optionally interrupted or terminated by one or more atoms or functional groups selected from the group consisting of S claim 3 , O claim 3 , NH claim 3 , C(O)O claim 3 , OC(O) claim 3 , C(O) claim 3 , NHC(O) claim 3 , and C(O)NH and wherein the linker is optionally substituted with one or more substituents independently selected from the group consisting of halogen claim 3 , OH claim 3 , NH claim 3 , C(O)H claim 3 , C(O)NH claim 3 , SOH claim 3 , NO claim 3 , and CN.5. (canceled)6. An immobilization product claim 1 , comprising the immobilization compound of immobilized on a solid support claim 1 , in particular wherein the solid support is selected from the group consisting of agarose claim 1 , modified agarose claim 1 , sepharose beads (e.g. NHS-activated sepharose) claim 1 , latex claim 1 , cellulose claim 1 , and ferro- or ferrimagnetic particles.7. A method for the identification of a methyltransferase interacting compound claim 1 , comprising the steps ofa) providing a protein preparation containing a variety of methyltransferases,{' ...

METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS

Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for reducing intraocular pressure comprising administering an effective amount of compounds of Formula I to a subject in need thereof. 118-. (canceled)19. A method of treating diseases and conditions caused by elevated intraocular pressure (IOP) in a human subject in need thereof by administering an effective amount of a selective adenosine Aagonist to an affected eye of the subject.20. The method of claim 19 , wherein the diseases and conditions caused by elevated IOP in a human are selected from the group consisting of normal-tension glaucoma claim 19 , ocular hypertension (OHT) claim 19 , and primary open-angle glaucoma (POAG).24. The method as claimed in wherein the selective adenosine Aagonist is selected from the group consisting of:((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate;((2R,3S,4R,5R)-5-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate;sodium ((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl sulfate; and((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-(tetrahydrofuran-3-ylamino)-9H-purin-9-yl)tetrahydrofuran-2-yl)methyl nitrate.25. The method as claimed in wherein the IOP of the affected eye is reduced by at least 10%.26. The method as claimed in wherein the IOP of the affected eye is reduced by about 10-20%.27. The method as claimed in wherein the IOP of the affected eye is reduced by 20% or more.28. The method as claimed in wherein the IOP of the affected eye is reduced by at least 10% for more than 3 hours.29. The method as claimed in wherein the IOP of the affected eye is reduced by about 10-20% for more than 3 hours.30. The method as claimed in wherein the IOP of the affected eye is reduced by 20% or more for more than 3 hours.31. The method as claimed in wherein the IOP of the affected eye ...

Modulators of Histone Methyltransferase, and Methods of Use Thereof

Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity. 35-. (canceled)79-. (canceled)11. The compound of claim 10 , wherein Ris hydrogen or alkyl.12. (canceled)13. The compound of claim 10 , wherein Ris hydrogen claim 10 , alkyl claim 10 , —O-alkyl claim 10 , halogen claim 10 , trifluoroalkyl claim 10 , —O-trifluoromethyl claim 10 , or —SO-trifluoromethyl.14. The compound of claim 13 , wherein Ris hydrogen claim 13 , alkyl claim 13 , halogen claim 13 , or trifluoroalkyl.15. The compound of claim 14 , wherein Ris hydrogen claim 14 , alkyl claim 14 , or halogen; and Ris hydrogen.16. (canceled)18. The compound of claim 17 , wherein Y is —NH— claim 17 , —N(alkyl)- claim 17 , —O— claim 17 , or —CH—.1922-. (canceled)23. The compound of claim 17 , wherein Ris aryl or aralkyl.2426-. (canceled)27. The compound of claim 17 , wherein Ris hydrogen or methyl.2853-. (canceled)5564-. (canceled)65. The compound of claim 1 , wherein Ris hydroxyl or hydrogen.66. (canceled)67. The compound of claim 1 , wherein Ris hydroxyl or hydrogen.68. (canceled)69. The compound of claim 1 , wherein Ris hydrogen or methyl.7094-. (canceled)95. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable diluent or carrier.96. A kit or packaged pharmaceutical comprising a compound of and instructions for use thereof.97. A method of treating or preventing a disorder in which DOT1-mediated protein methylation plays a part claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of .98. The method of claim 97 , wherein the disorder is cancer or a neurological disorder.99. (canceled) This application claims priority to, and the benefit of, U.S. provisional application No. 61/419,591, filed Dec. 3, 2010, the content of ...

METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided. 130-. (canceled)31. A method for the treatment of a hepatitis C virus infection in a host , comprising administering to said host an anti-virally effective amount of a β-D-2′-methyl nucleoside or a phosphate thereof , or a pharmaceutically acceptable salt or ester thereof.32. The method of claim 31 , wherein an anti-virally effective amount of a β-D-2′-methyl nucleoside or a phosphate thereof claim 31 , or a pharmaceutically acceptable ester thereof is administered.33. The method of claim 32 , wherein the nucleoside is a pyrimidine nucleoside.34. The method of claim 33 , wherein the J3-D-2′-methylpyrimidine nucleoside is administered in combination or alternation with a second anti-hepatitis C agent.35. The method of claim 34 , wherein the second anti-hepatitis C agent is an interferon.36. The method of claim 34 , wherein the second anti-hepatitis C agent is ribavirin.37. The method of claim 34 , wherein the second anti-hepatitis C agent is an interferon claim 34 , ribavirin or a combination thereof.38. The method of claim 31 , wherein the nucleoside is a pyrimidine nucleoside.39. The method of claim 38 , wherein the β-D-2′-methylpyrimidine nucleoside is administered in combination or alternation with a second anti-hepatitis C agent.40. The method of claim 39 , wherein the second anti-hepatitis C agent is an interferon.41. The method of claim 39 , wherein the second anti-hepatitis C agent is ribavirin.42. The method of claim 39 , wherein the second anti-hepatitis C agent is an interferon claim 39 , ribavirin or a combination thereof.43. The method of claim 31 , wherein the β-D-2′-methyl nucleoside or a phosphate thereof claim 31 , or a pharmaceutically acceptable salt or ester thereof is in a tablet or capsule.44. ...

Methods and compositions for treating flaviviridae infections

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Beta-l-2'-deoxy-nucleosides for the treatment of hepatitis b

This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-β-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2′-deoxy-β-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.

NOVEL ANTIBACTERIAL COMPOUNDS

The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim . The compounds are useful in the prevention and/or treatment of bacterial infections. 3: The compound of claim 2 , wherein Xis —O— or —NH—.5: The compound of claim 1 , wherein Xis —CH—.6: The compound of claim 1 , wherein Ris NHor OH.7: The compound of claim 1 , wherein Ris H.8: The compound of claim 1 , wherein Ris H.9: The compound of any claim 1 , wherein Ris H.10: The compound of claim 1 , wherein Ris H.11: The compound of wherein the compound is 5′-amino-5′-deoxyadenosin-8-yl-thio-N-[(5′-amino-5′-deoxyadenosine)methyl]acetamide; 8-[3-N-(5′-deoxyadenosyl)aminoprop-1-ynyl]adenosine; 8-[3-(5′-deoxyadenosyl)methoxyprop-1-ynyl]adenosine claim 1 , or any combination thereof.12: A pharmaceutical composition comprising the compound of claim 1 , in admixture with one or more pharmaceutically acceptable excipients.13: The compound of claim 1 , wherein the compound is suitable for prevention claim 1 , treatment claim 1 , or both prevention and treatment of a bacterial infection.16: A chemical probe comprising the compound of claim 1 , coupled to a detectable label.17. (canceled)18: A method for screening a molecule inhibiting NAD kinase claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'contacting NAD kinase with the chemical probe of with a molecule to be screened;'}determining a quantity of chemical probe bound or unbounded to the NAD kinase; anddeducing from the quantity if the molecule is an inhibitor of the NAD kinase.19: A method of treating a bacterial infection claim 1 , the method comprising administering the compound of to a subject in need thereof. The present invention relates to compounds for use in the prevention and/or treatment of bacterial infections, pharmaceutical compositions comprising them, and processes for the preparation thereof.The search for new antibacterial compounds has become ...

Nucleobase-functionalized conformationally restricted nucleotides and oligonucleotides for targeting nucleic acids

Embodiments are disclosed herein that involve C5-functionalized nucleic acids, which can be used for detecting a target in a nucleic acid. Particular embodiments disclose methods for making these compounds, wherein the compounds can be formed by coupling of an intermediate with a linker. Certain embodiments disclose the use of these compounds for detecting single nucleotide polymorphisms, and for increasing the thermal affinity of nucleic acid complements as compared to unmodified nucleic acid complements. In addition, the disclosed compounds can decrease enzymatic degradation of nucleic acids.

SUBSTITUTED PYRROLO]2,3-D]PYRIMIDINES

The present disclosure relates to compounds of formula (I-A) using the compounds 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , characterized by one or more of the following features:(a) X is —O—;{'sub': '2', '(b) Y is —O— or —CH—;'}{'sup': '3a', '(c) Ris —OH;'}{'sup': 3b', '3, 'sub': '1-4', '(d) Rand Rare each independently hydrogen or Caliphatic;'}{'sup': 3', '5, '(e) Ris hydrogen, fluoro, or —OR;'}{'sup': 5', '5′, '(f) Rand Rare each hydrogen;'}{'sup': '4', '(g) each Ris hydrogen;'}{'sup': '2', '(h) each Ris hydrogen;'}{'sup': 'h', '(i) Ris hydrogen;'}{'sup': 'j', '(j) Ris hydrogen; and'}{'sup': 'k', 'sub': '1-4', '(k) Ris hydrogen, halo, or Caliphatic.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , characterized by one or more of the features (a) through (f):{'sup': '3a', 'sub': 1-4', '1-4, '(a) Ris hydrogen, hydroxy, methoxy, Caliphatic, Cfluoroaliphatic, or fluoro;'}{'sup': '3', '(b) Ris hydrogen;'}{'sup': '3', '(c) Ris hydrogen or hydroxy;'}{'sup': '3d', '(d) Ris hydrogen;'}{'sup': '4', '(e) each Ris hydrogen; and'}{'sup': '5', '(f) Ris hydrogen.'}9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein Ring B is a phenyl ring substituted with 0-2 substituents independently selected from the group halo claim 8 , —OH claim 8 , —O(Calkyl) claim 8 , —CN claim 8 , —N(R) claim 8 , —C(O)(Calkyl) claim 8 , —COH claim 8 , —CO(Calkyl) claim 8 , —C(O)N H claim 8 , —C(O)NH(Calkyl) claim 8 , —Caliphatic claim 8 , —Cfluoroaliphatic claim 8 , —O(Cfluoroaliphatic) claim 8 , optionally substituted aryl claim 8 , and optionally substituted heteroaryl.10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 1', '12a', '12b', '12a', '12b', '12a', '12d, 'sub': '1-10', 'Ris Caliphatic, —Z—R, —Z—R, -L-Z—R, -L-Z—R, -L-Ror -L-R;'}{'sup': 13', '3, 'L is —C(R)═C(R)— or —C≡C—; and'}{'sup': 12d', '15', '15', '16', '14', '14', '16, ...

NOVEL COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 2. The compound of claim 1 , wherein:X is N.3. The compound of claim 1 , wherein:W is S or O.5. The compound of claim 4 , wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00008', '@he': '2.12mm', '@wi': '4.57mm', '@file': 'US20140005136A1-20140102-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'represents a carbon-carbon double bond; and'}{'sup': 'P', 'Ris cyclopropyl.'}6. The compound of claim 1 , wherein:X is N;W is S; and{'sup': '1', 'sub': 3', '2', '2, 'Ris Cl, Br, I, optionally substituted methyl, CF, CHFor CHF.'}7. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are not H.'}8. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are H.'}9. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O.'}10. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring.'}12. The compound of claim 11 , wherein:{'sup': '1a', 'Ris at least one amino acid.'}13. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a peptide.'}14. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a lipid.'}15. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a phospholipid.'}16. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a glycoside.'}17. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleoside.'}18. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleotide.'}19. The compound of claim 11 , wherein:{'sup': '1a', 'Ris an oligonucleotide.'}20. The compound of claim 11 , wherein:{'sup': ...

Ribofuranosyl Purine Compounds, Methods for Preparing the Same and Use Thereof

The present invention relates to the compounds of the formulae (I) and (I-1) and the process for preparing the same, uses of the compounds for the treatment of diseases associated with platelet aggregation and in the manufacture of a medicament for the treatment of diseases associated with platelet aggregation, and relates to a pharmaceutical composition and a pharmaceutical formulation containing the compounds, wherein the definitions of R, R, Rand Rin the formulae are the same as those in the description. 2. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rrepresents an unsubstituted or R-substituted C-Calkyl claim 1 , wherein Rrepresents halogen claim 1 , C-Calkyl claim 1 , C-Calkoxyl claim 1 , halogenated C-Calkyl claim 1 , halogenated C-Calkoxyl claim 1 , hydroxyl claim 1 , hydroxyl C-Calkyl claim 1 , carboxyl claim 1 , nitro claim 1 , cyano claim 1 , C-Calkylthio claim 1 , or C-Calkyl-CO—.3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rrepresents an unsubstituted or R-substituted C-Calkyl claim 1 , an unsubstituted or R-substituted C-Ccycloalkyl claim 1 , an unsubstituted or R-substituted 5- to 6-membered heteroaryl-C-Calkyl claim 1 , an unsubstituted or R-substituted phenyl-C-Calkyl claim 1 , or an unsubstituted or R-substituted 5- to 6-membered heterocyclyl-C-Calkyl claim 1 , wherein Ris selected from the group consisting of C-Calkyl claim 1 , C-Calkoxyl claim 1 , hydroxyl claim 1 , hydroxyl C-Calkyl claim 1 , carboxyl claim 1 , nitro claim 1 , cyano claim 1 , C-Calkylthio and C-Calkyl-CO—; and Ris selected from the group consisting of halogen claim 1 , C-Calkyl claim 1 , C-Calkoxyl claim 1 , hydroxyl claim 1 , hydroxyl C-Calkyl claim 1 , carboxyl claim 1 , nitro claim 1 , cyano claim 1 , C-Calkylthio claim 1 , and C-Calkyl-CO—.4. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rrepresents C-Calkyl; Rrepresents C-Calkyl claim 1 , ...

1,2,3-Triazolyl Purine Derivatives

The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections. An example of a 1,2,3-triazolyl purine derivative of the invention is

METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS

Provided herein is a method of reducing intraocular pressure (IOP) in humans using N6-cyclopentyladenosine (CPA), CPA derivatives or prodrugs or enhanced cornea permeability formulations of CPA. In one embodiment, the invention is directed to CPA derivatives or prodrugs that are permeable to the cornea. In another embodiment, the invention is directed to uses of certain compounds in human subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT). 116-. (canceled)18. The method of claim 17 , wherein about 20 μg to about 700 μg of a compound of Formula II or a pharmaceutically acceptable salt thereof claim 17 , is administered to an affected eye of the human subject.19. The method of claim 17 , wherein the compound is administered from 1 to 4 times daily.20. The method of claim 18 , wherein the compound is administered from 1 to 2 times daily.21. The method of claim 17 , wherein about 350 μg of a compound of Formula II claim 17 , or a pharmaceutically acceptable salt thereof claim 17 , is administered from 1 to 2 times daily.23. The method of claim 22 , wherein about 0.05 mg/ml to about 7.0 mg/ml of a compound of Formula II claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , is administered to an affected eye of the human subject.24. The method of claim 22 , wherein about 20 μg to 700 μg of a compound of Formula II claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , is administered to an affected eye of the human subject.25. The method of claim 23 , wherein the compound is administered from 1 to 4 times daily.26. The method of claim 24 , wherein the compound is administered from 1 to 2 times daily.27. The method of claim 22 , wherein about 350 μg of a compound of Formula II claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , is administered from 1 to 2 times daily.32. The method of or claim 22 , wherein Ris selected from —(CO)CH(CH) claim 22 ...

6-ETHER/THIOETHER-PURINES AS TOPOISOMERASE II CATALYTIC INHIBITORS AND THEIR USE IN THERAPY

The present invention relates to certain purines, which act as topoisomerase II catalytic inhibitors. These compounds are useful in combination with topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). These compounds are useful in the treatment of tissue damage associated with extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin. 2104.-. (canceled) This application is related to: United Kingdom patent application 0502573.9 filed 8 Feb. 2005, the contents of which are incorporated herein by reference in their entirety.The present invention relates to topoisomerase II catalytic inhibitors, and their use in therapy. In particular, the present invention relates to certain purines (6-ether/thioether-purines) and derivatives thereof for use in combination with cytostatic agents that act as topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). The present invention also relates to use of these compounds in the treatment of tissue damage associated with accidental extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin.A number of patents and publications are cited herein in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Each of these references is incorporated herein by reference in its entirety into the present disclosure, to the same extent as if each individual reference was specifically and individually indicated to be incorporated by reference.Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising,” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or ...

N-ALKYL 2-(DISUBSTITUTED)ALKYNYLADENOSINE-5-URONAMIDES AS A2A AGONISTS

The present invention provides N-alkyl 2-(disubstituted)alkynyladenosine-5′-uronamides and derivatives thereof and pharmaceutical compositions containing the same that are selective agonists of Aadenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents. 3. A compound of claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 2 , wherein:R is selected from: methyl, ethyl, and cyclopropyl;{'sup': '1', 'Ris H;'}{'sup': '2', 'Ris selected from: H, methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopropyl-methylene, cyclobutyl, cyclobutyl-methylene, cyclopentyl, and methoxy-ethylene;'}ring A is selected from: phenyl, pyridyl, and thienyl;{'sup': '3', 'ring A is optionally substituted with 1-2 Rgroups;'}{'sup': 3', 'a', 'a', 'a', 'b', 'a', 'a', 'a', 'b', 'a', 'b, 'sub': 1-4', '3', '3', '2', 'p, 'Ris independently selected from: Calkyl, F, Cl, Br, I, —CN, OR, SR, NRR, CF, OCF, COR, COR, C(O)NRR, and S(O)NRR;'}{'sup': 'a', 'sub': '1-4', 'Ris independently selected from: H and Calkyl;'}{'sup': 'b', 'sub': '1-4', 'Ris independently selected from: H and Calkyl; and,'}p is independently selected from: 0, 1, and 2.4. A compound of claim 3 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 3 , wherein:R is selected from: methyl, ethyl, and cyclopropyl;{'sup': '1', 'Ris H;'}{'sup': '2', 'Ris selected from: methyl, isobutyl, cyclopropyl, cyclopropyl-methylene, cyclobutyl, cyclopentyl, and methoxy-ethylene;'}ring A is selected from: phenyl, pyridyl, and thienyl;{'sup': '3', 'ring A is optionally substituted with 1-2 Rgroups;'}{'sup': 3', 'a, 'sub': 1-4', '3', '3, 'Ris independently selected from: Calkyl, F, Cl, —CN, OR, CF, and OCF;'}{'sup': 'a', 'sub': '1-4', 'Ris independently selected from: H and Calkyl; and,'}{'sup': 'b', 'sub': '1-4', 'Ris independently selected from: H and Calkyl.'}5. A compound of claim 4 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 4 , wherein:R is ...

Processes for the preparation of regadenoson and a new crystalline form thereof

This disclosure relates to an improved process for the preparation of regadenoson, pharmaceutically acceptable salts thereof, and hydrates thereof, and for the preparation of intermediates useful in the synthesis of regadenoson. The disclosure also relates to a new crystalline form of regadenoson. Processes for the preparation of the crystalline form, compositions containing the crystalline form, and methods of use thereof are also described.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment uses, and processes for preparing each of which utilize the compound represented by formula I.

DIARYLSULFIDE BACKBONE CONTAINING PHOTOLABILE PROTECTING GROUPS

The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis. 2. The compound according to wherein R1 is a phenyl-group claim 1 , a tert-butyl-phenyl group claim 1 , a 1- or 2-naphthyl-group claim 1 , a 2-pyridyl-group an aminophenyl-group claim 1 , an N-alkylaminophenyl-group claim 1 , an N-Acylaminophenyl-group claim 1 , a carboxyphenyl-group claim 1 , a phenylcarboxylic ester or an amide.3. The compound according to wherein A is —CH(CH)—CH—.4. The compound according to wherein R2 is a phosphoramidite or —P(OCHCHCN)(N-iPr).5. The compound according to wherein R3 is H or an ethyl group.6. The compound according to wherein R4 is H and R5 is H.7. The compound according to wherein B is selected from the group consisting of adenine claim 1 , cytosine claim 1 , guanine claim 1 , thymine or uracil.8. The compound according to wherein when B is adenine claim 1 , cytosine or guanine the protecting group is phenoxyacetyl- claim 1 , 4-tert-butyl-phenoxyacetyl- claim 1 , 4-isopropyl-phenoxyacetyl- or dimethylformamidino-residues claim 1 , when B is adenine the protecting group is benzoyl- or p-nitro-phenyl-ethoxy-carbonyl-(p-NPPOC)-residues claim 1 , when B is guanine the protecting group is isobutyroyl- claim 1 , p-nitrophenylethyl (p-NPE) or p-NPEOC-residues and when B is cytosine the protecting group is benzoyl- claim 1 , isobutyryl- or p-NPEOC-residues.9. The compound according to wherein R7 is a natural amino acid.10. A method for preparing a diarylsulfide backbone containing one or more photolabile protecting group(s) according to comprising the steps ofa) Provision of p-diethylbenzene as a starting material;b) Bromination of the phenylring;c) Nitration of the obtained compound in Nitric- and Sulfuric Acid in the position para- to the Bromine;d) Purification and crystallization;e) ...

Substituted Purine and 7-Deazapurine Compounds

The present invention relates to substituted purine and 7-deazapurine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. 2. The compound of claim 1 , wherein A is O.3. The compound of claim 1 , wherein A is O and m is 2.4. The compound of claim 1 , wherein X is N.5. The compound of claim 1 , wherein Q is NHor NHR claim 1 , in which Ris -M-T claim 1 , Mbeing a bond or C-Calkyl linker and Tbeing C-Ccycloalkyl.6. The compound of claim 1 , wherein Rand R claim 1 , are each H.7. The compound of claim 1 , wherein Y is R.8. The compound of claim 7 , wherein Ris C-Calkyl optionally substituted with C-Ccycloalkyl or halo.9. The compound of claim 7 , wherein Ris C-Ccycloalkyl optionally substituted with C-Calkyl or halo.10. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Ris halo claim 1 , C-Calkoxyl optionally substituted with one or more halo; C-Calkylsulfonyl optionally substituted with one or more halo; C-Calkyl optionally substituted with one or more substituents selected from CN claim 1 , halo claim 1 , C-Ccycloalkyl claim 1 , hydroxy claim 1 , and C-Calkoxyl; C-Ccycloalkyl optionally substituted with one or more C-Calkyl or CN; or 4 to 8-membered heterocycloalkyl optionally substituted with one or more substituents selected from CN claim 1 , halo claim 1 , hydroxy claim 1 , C-Calkyl and C-Calkoxyl.11. The compound of claim 10 , wherein at least one of R claim 10 , R claim 10 , R claim 10 , and Ris selected from the group consisting of F; Cl; Br; CF; OCF; SOCF; oxetanyl optionally substituted with one or more substituents selected from CN claim 10 , halo claim 10 , hydroxy claim 10 , C-Calkyl and C-Calkoxyl; C-Ccycloalkyl optionally substituted with one ...

2'-O-AMINOOXYMETHYL NUCLEOSIDE DERIVATIVES FOR USE IN THE SYNTHESIS AND MODIFICATION OF NUCLEOSIDES, NUCLEOTIDES AND OLIGONUCLEOTIDES

Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R-Rare as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2′-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2′-O-(2-cyanoethyl)oxymethyl or 2′-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions. 2. The compound of claim 1 , wherein the optionally protected nucleobase or the nucleobase is selected from the group consisting of cytosine claim 1 , adenine claim 1 , guanine claim 1 , uracil claim 1 , thymine claim 1 , xanthine claim 1 , hypoxanthine claim 1 , alkyl derivatives thereof claim 1 , amino derivatives thereof claim 1 , halo derivatives thereof claim 1 , 2- or 8-amino adenine claim 1 , 2- or 8-alkyl adenine claim 1 , 5-halo uracil claim 1 , 5-halo cytosine claim 1 , 2 claim 1 ,6-diaminopurine claim 1 , 6-aza uracil claim 1 , 4-thio uracil claim 1 , 5-trifluoromethyl uracil claim 1 , 5-trifluoromethyl cytosine claim 1 , 6-aza thymine claim 1 , 6-thioguanine claim 1 , 7-deazaadenine claim 1 , 7-deazaguanine claim 1 , 8-mercapto adenine claim 1 , 8-thioalkyl adenine claim 1 , 8-hydroxyl/oxo adenine claim 1 , 8-mercapto guanine claim 1 , 8-thioalkyl guanine claim 1 , and 8-hydroxyl/oxo guanine claim 1 , 1-methyladenine claim 1 , 2-methyladenine claim 1 , N-methyladenine claim 1 , N-isopentyladenine claim 1 , 2-methylthio-N-isopentyladenine claim 1 , N claim 1 ,N-dimethyladenine claim 1 , 8-bromoadenine claim 1 , 2-thiocytosine claim 1 , 3-methylcytosine claim 1 ...

MODIFIED NUCLEOSIDES FOR THE TREATMENT OF VIRAL INFECTIONS AND ABNORMAL CELLULAR PROLIFERATION

The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. 1358.-. (canceled) This application claims priority to U.S. provisional application No. 60/241,488, filed Oct. 18, 2000 and U.S. provisional application No. 60/282,156, filed on Apr. 6, 2001.The present invention includes compounds and methods for the treatment of Flaviviridae, Orthomyxoviridae, Paramyxoviridae infections and abnormal cellular proliferation.The Flaviviridae is a group of positive single-stranded RNA viruses with a genome size from 9-15 kb. They are enveloped viruses of approximately 40-50 nm. An overview of the Flaviviridae taxonomy is available from the International Committee for Taxonomy of Viruses. The Flaviviridae consists of three genera.One of the most important Flaviviridae infections in humans is caused by the hepatitis C virus (HCV). This is the second major cause of viral hepatitis, with an estimated 170 million carriers world-wide (World Health Organization; Hepatitis C: global prevalence, 1997, 72, 341), 3.9 million of whom reside in the United States (Centers for Disease Control; unpublished data, http://www.cdc.gov/ncidod/diseases/hepatitis/heptab3.htm).The genomic organization of the Flaviviridae share many common features. The hepatitis C virus (HCV) genome is often used as a model. HCV is a small, enveloped virus with a positive single-stranded RNA genome of ˜9.6 kb within the nucleocapsid. The genome contains a single open reading frame (ORF) encoding a polyprotein of just over 3,000 amino acids, which is cleaved to generate the mature structural and nonstructural viral proteins. The ORF is flanked by 5′ and 3′ non- ...

Substituted 6-(Benzylamino) Purine Riboside Derivatives, Use Thereof and Compositions Containing These Derivatives

A method of treatment using 2-substituted-6-(substituted benzylamino)purine riboside derivatives of the general formula I. These compounds possess antiapoptotic, anti-inflammatory and differentiating activities. 2. The method of wherein the 2-substituted-6-(substituted benzylamino)purine riboside derivatives of the general formula I are selected from the group comprising 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , mercapto claim 1 , methyl claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino(C-C)alkylamino)-6-(2-hydroxy-3-methoxybenzylamino)purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , mercapto claim 1 , methyl claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino(C-C)alkylamino)-6-(2-hydroxy-4-methoxybenzylamino)purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , mercapto claim 1 , methyl claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino (C-C)alkylamino)-6-(2-hydroxy-5-methoxybenzylamino)-purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , mercapto claim 1 , methyl claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino(C-C)alkylamino)-6-(2-hydroxy-6-methoxybenzylamino)purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , mercapto claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino(C-C)alkylamino)-6-(2 claim 1 ,3-dihydroxy-4-methoxybenzylamino)purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , methyl claim 1 , mercapto claim 1 , C-C-alkylmercapto claim 1 , C-C-alkylamino claim 1 , hydroxy(C-C)alkylamino claim 1 , amino(C-C)alkylamino)-6-(2 claim 1 ,5-dihydroxy-4-methoxy-benzylamino)purine riboside claim 1 , 2-(amino claim 1 , chloro claim 1 , fluoro claim 1 , methyl claim 1 , ...

N-Pyrazole A2A Receptor Agonists

2-adenosine N-pyrazole compounds having the following formula: 17.-. (canceled)9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical excipient is selected from the group consisting of polyvinylpyrrolidinone claim 8 , gelatin claim 8 , hydroxycellulose claim 8 , acacia claim 8 , polyethylene glycol claim 8 , mannitol claim 8 , sodium chloride claim 8 , and sodium citrate.10. The pharmaceutical composition of claim 8 , wherein the aqueous buffered solution is an isotonic solution.11. The pharmaceutical composition of claim 10 , wherein the aqueous buffered solution comprises isotonic saline solution claim 10 , 5% dextrose in water claim 10 , buffered sodium acetate solution claim 10 , or buffered ammonium acetate solution.12. The pharmaceutical composition of claim 8 , wherein the aqueous buffered solution comprises a liquid carrier selected form the group consisting of peanut oil claim 8 , olive oil claim 8 , glycerin claim 8 , saline claim 8 , one or more alcohols claim 8 , and water.13. The pharmaceutical composition of claim 12 , wherein the liquid carrier comprises glycerol monostearate claim 12 , glycerol monostearate with a wax claim 12 , glycerol distearate claim 12 , or glycerol distearate with a wax.14. The pharmaceutical composition of suitable for parenteral administration.15. The pharmaceutical composition of suitable for intravenous administration.16. The pharmaceutical composition of suitable for continuous infusion or bolus.17. The pharmaceutical composition of suitable for oral administration.19. The pharmaceutical composition of claim 18 , wherein the powder comprises a solid carrier selected form the group consisting of starch claim 18 , lactose claim 18 , calcium sulfate dihydrate claim 18 , teffa alba claim 18 , magnesium stearate claim 18 , stearic acid claim 18 , talc claim 18 , pectin claim 18 , acacia claim 18 , agar claim 18 , and gelatin.20. The pharmaceutical composition of claim 19 , wherein the solid carrier comprises ...

2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′-chloro nucleosides according to Formula 2001: 4. The compound of wherein each X is independently an N-linked amino acid claim 1 , or a derivative thereof.5. The compound of wherein each X is independently an N-linked L-amino acid claim 1 , or a derivative thereof.6. The compound of wherein each X is independently an N-linked D-amino acid claim 1 , or a derivative thereof.7. The compound of wherein each X is independently an N-linked D-alanine claim 1 , or a derivative thereof.8. (canceled)9. (canceled)10. The compound of wherein:W is O;{'sup': 1', '1', '2, 'each X is independently —ORor —NRR;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '1', 'sub': p', '3', 'p', 'p', '3', 'p', '3', 'p', '3', 'p', '3', '2, 'each Ris independently -(L)CR, -(L)Ar, -LC(O)O(L)CR, -LSC(O)(L)CR, -LOC(O)(L)CR, -LOC(O)(L)Cy, -LSC(O)LNHC(O)OCR, -LSC(O)LOC(O)LNH, -LC(O)LOAr, -LC(O)OLAr, or -LSC(O)LOH;'}each L is independently alkylene;each R is independently hydrogen, alkyl, aryl, or heteroaryl;each Ar is independently aryl, or heteroaryl;each Cy is independently cycloalkyl; andeach p is independently 0 or 1.1119-. (canceled)21. (canceled)22. (canceled)24. The compound of wherein Ris alkylamino.26. (canceled)2933-. (canceled)34. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient claim 1 , carrier or diluent.35. (canceled)36. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising the administration of an effective treatment amount of a compound of .37. (canceled)38. The method of claim 36 , wherein the administration directs a substantial amount of the compound claim 36 , ...

Selective inhibitors of histone methyltransferase dot1l

Structure and mechanism based design was used to design potent ribose containing inhibitors of DOT1L with IC 50 values as low as 38 nM. These ribose containing inhibitors exhibit only weak or no activities against four other representative histone lysine and arginine methyltransferases, G9a, SUV39H1, PRMT1 and CARM1.

PYRROLOPYRIMIDINE NUCLEOSIDES AND ANALOGS THEREOF

The present disclosure provides pyrrolopyrimidine nucleoside analogs of the Formula I, Formula IA, Formula IB, or Formula II and phospholipid conjugates and pharmaceutical compositions thereof wherein Rand A are defined herein. Also presented are methods of treating and/or preventing viral infection and/or viral infection-associated disease or disorder with one or more compounds of Formula I, Formula IA, Formula IB, or Formula II. 121.-. (canceled)341. A pharmaceutical composition comprising the compound of claim , or a pharmaceutically acceptable salt , solvate , enantiomer , diastereomer , racemate , or mixture thereof , and a pharmaceutically acceptable carrier. This application is a continuation of U.S. Ser. No. 16/533,194, filed Aug. 6, 2019, which is a continuation of U.S. Ser. No. 15/599,056, filed May 18, 2017 (now U.S. Pat. No. 10,407,457 issued on Sep. 10, 2019), which is a continuation of U.S. Ser. No. 15/358,938, filed Nov. 22, 2016 (now U.S. Pat. No. 9,701,706 issued on Jul. 11, 2017), which is a continuation of U.S. Ser. No. 15/231,528, filed Aug. 8, 2016 (now U.S. Pat. No. 9,708,359 issued on Jul. 18, 2017), which claims priority to and the benefit of U.S. Provisional Application No. 62/202,010, filed Aug. 6, 2015, and to U.K. Application No. 1606645.8, filed Apr. 15, 2016, the entire contents of each of which are incorporated by reference herein in their entireties.This invention was made with government support under Grant Number 5 U19-AI-03 1 718 (National Cooperative Drug Discovery Group for Opportunistic Infections: New Inhibitors and New Targets to Develop HCMV Drugs), awarded by the National Institute of Allergy and Infectious Diseases. The government has certain rights in the invention.The contents of the text file named “CHIM-830_C02US_ST25.txt”, which was created on May 4, 2017 and is 2.18 KB in size, are hereby incorporated by reference in their entireties.This application relates to pyrrolopyrimidine nucleoside analogs and phospholipid ...

Protected Monomer and Method of Final Deprotection for RNA Synthesis

A method of deprotecting a solid support bound polynucleotide includes the step of contacting the polynucleotide with a composition comprising a diamine under conditions sufficient to deprotect the 2′-protected ribonucleotide residue. The solid support bound polynucleotide has at least one 2′-protected ribonucleotide residue, which has the following structure: wherein B P is a protected or unprotected heterocycle; R 12 is a protecting group selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl, and a substituted aryl; X is O or S; and PG is a thionocarbamate protecting group.

CRYSTAL FORM OF REGADENOSON AND PREPARATION METHOD THEREOF

The present invention relates to the field of medicinal chemistry, and discloses a new crystal form of regadenoson, i.e., a crystal form E of regadenoson, as well as a method for preparing the new crystal form of regadenoson. The crystal form E of regadenoson according to the present invention has excellent performances in terms of radionuclide myocardial perfusion imaging, and has a poor toxicity, good storage stability, and can be used in the preparation of a medicament used as a stress agent for radionuclide myocardial perfusion imaging. 1. A crystal form E of regadenoson , which is characterized in that , it has an X-ray powder diffraction pattern substantively as shown in .2. The crystal form E according to claim 1 , which is characterized in that claim 1 , there are absorption peaks at 3331.71 claim 1 , 3215.54 claim 1 , 2927.97 claim 1 , 1648.75 claim 1 , 1604.99 claim 1 , 1577.42 claim 1 , 1530.74 claim 1 , 1492.24 claim 1 , 1447.33 claim 1 , 1409.03 claim 1 , 1380.47 claim 1 , 1343.48 claim 1 , 1286.87 claim 1 , 1234.77 claim 1 , 1205.30 claim 1 , 1188.55 claim 1 , 1125.28 claim 1 , 1092.61 claim 1 , 1060.80 claim 1 , 1025.93 claim 1 , 983.13 claim 1 , 910.61 claim 1 , 866.49 claim 1 , 810.21 claim 1 , 791.76 claim 1 , 725.68 claim 1 , 663.00 claim 1 , 632.69 claim 1 , 511.09 and 410.05 cmin infrared spectrum thereof.3. The crystal form E according to claim 1 , which is characterized in that claim 1 , there is an absorption peak at about 221.02° C. in differential scanning calorimetric analysis curve thereof.4. A method for preparing the crystal form E of regadenoson according to claim 1 , characterized by dissolving regadenoson in N claim 1 ,N-dimethylformamide claim 1 , adding a suitable amount of a polar solvent claim 1 , and then concentrating under reduced pressure claim 1 , to obtain the crystal form E of regadenoson.5. The preparation method according to claim 4 , which is characterized in that claim 4 , the polar solvent is dichloromethane claim 4 , ...

LABELLED NUCLEOTIDES

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a Csubstituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a Csubstituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside). 160-. (canceled)61. A nucleoside or nucleotide comprising a base attached to a detectable label via a phosphine cleavable linker comprising a disulfide.62. The nucleoside or nucleotide of claim 61 , wherein the nucleoside or nucleotide further comprises a dideoxyribose moiety.63. The nucleoside or nucleotide of claim 61 , wherein the nucleoside or nucleotide further comprises a ribose or deoxyribose moiety with a hydroxyl protecting group attached to the 2′ or 3′ oxygen atom.64. The nucleoside or nucleotide of claim 63 , wherein the linker and protecting group are cleavable under the same conditions.65. The nucleoside or nucleotide of claim 63 , wherein the protecting group is azidomethyl.66. The nucleoside or nucleotide of claim 61 , wherein the base is a purine claim 61 , pyrimidine or deazapurine.67. The nucleoside or nucleotide of claim 61 , wherein the detectable label is a fluorophore.68. An oligonucleotide comprising the nucleoside or nucleotide of .69. The oligonucleotide of claim 68 , wherein the oligonucleotide is attached to a solid support.70. A solid support comprising the oligonucleotide of .71. A composition comprising four nucleosides or nucleotides claim 68 , wherein each nucleoside or nucleotide comprises a base attached to a detectable label via a phosphine cleavable linker comprising a disulfide claim 68 , wherein each nucleoside or nucleotide carries a different detectable label.72. ...

Process for preparation of regadenoson and polymorphs thereof

The present invention relates to a process for preparation of Regadenoson and polymorphs thereof. In particular, the present invention relates to a process for preparation of Regadenoson Form C.

MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided. 1. A compound having the formulaor a pharmaceutically acceptable salt thereof. This application is a continuation application of U.S. application Ser. No. 16/273,843, filed Feb. 2, 2019, which is a continuation application of U.S. application Ser. No. 15/400,748, filed Jan. 6, 2017, now U.S. Pat. No. 10,239,912, which claims priority benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/276,564, filed Jan. 8, 2016 and U.S. Provisional Application No. 62/324,077, filed Apr. 18, 2016, each of which is herein incorporated by reference in its entirety for all purposes.Not ApplicableNot ApplicableProvided herein are, for example, compounds and compositions for inhibition of adenosine by 5′-nucleotidase, ecto, also known as CD73, and pharmaceutical compositions comprising same. Also provided herein are, for example, methods of treating or preventing a disease, disorder or condition, or a symptom thereof, mediated by inhibition of adenosine by 5′-nucleotidase, ecto.Purinergic signaling, a type of extracellular signaling mediated by purine nucleotides and nucleosides such as ATP and adenosine, involves the activation of purinergic receptors in the cell and/or in nearby cells, resulting in the regulation of cellular functions. Most cells have the ability to release nucleotides, which generally occurs via regulated exocytosis (see Praetorius, H. A.; Leipziger, J. (1 Mar. 2010) 72(1): 377-393). The released nucleotides can then be hydrolyzed extracellularly by a variety of cellular membrane-bound enzymes referred to as ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection, with a nucleoside, a nucleotide and an analog thereof. 2. The compound of claim 1 , wherein Ris azidomethyl.3. The compound of claim 1 , wherein Ris aminomethyl.5. The compound of claim 4 , wherein Rand Rare both hydrogen or absent.6. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. The compound of claim 4 , wherein Ris an optionally substituted aryl; and Ris an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. The compound of claim 4 , wherein Rand Rare both an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.30. (canceled)31. (canceled)32. (canceled)34. The compound of claim 33 , wherein m is 0 claim 33 , and Rand Rare independently absent or hydrogen.35. The compound of claim 33 , wherein m is 1 claim 33 , and R claim 33 , Rand Rare independently absent or hydrogen.36. The compound of claim 1 , wherein Ris H.37. The compound of claim 1 , wherein Ris an optionally substituted acyl.38. The compound of claim 1 , wherein Ris an optionally substituted O-linked amino acid.39. (canceled)42. (canceled)45. (canceled)46. (canceled)47. The compound of claim 1 , wherein Ris OH.48. The compound of claim 1 , wherein Ris —OC(═O)R.49. The compound of claim 1 , wherein Ris O-linked amino acid.50. (canceled)51. The compound of claim 1 , wherein Ris hydrogen.52. (canceled)53. (canceled)54. The compound of claim 1 , wherein ...

CYCLIC PEROXIDES AS PRODRUGS FOR SELECTIVE DELIVERY OF AGENTS

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. 24.-. (canceled)622.-. (canceled)23. The compound of claim 1 , wherein each Lis independently selected from a bond or substituted or unsubstituted arylene.24. (canceled)25. The compound of claim 1 , wherein each Lis independently selected from a bond claim 1 , substituted or unsubstituted alkylene claim 1 , or substituted or unsubstituted heteroalkylene.26. (canceled)27. The compound of claim 1 , wherein each -L-L- is independently a bond claim 1 , -Ph-(CH)— or -Ph(CH)—OC(O)—; and w is an integer 1 to 4.2831.-. (canceled)32. The compound of claim 1 , wherein the drug moiety is independently a monovalent radical of an anti-infective agent.33. The compound of claim 32 , wherein the anti-infective agent is an anti-parasitic agent.34. The compound of claim 32 , wherein the anti-infective agent is an anti-malarial drug.35. The compound of claim 32 , wherein the anti-infective agent is an anti-bacterial drug.36. The compound of claim 1 , wherein the drug moiety is independently a monovalent radical of an anti-cancer drug.37. The compound of claim 1 , wherein the detectable moiety is independently a monovalent radical of a fluorophore.38. The compound of claim 1 , wherein the protein moiety is independently a monovalent radical of an antibody.39. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of .40. A method of treating a disease in a patient in need of such treatment claim 1 , said method comprising administering a therapeutically effective amount of a compound of to said patient.41. (canceled)42. The method of claim 40 , wherein ...

Cyclic Di-Nucleotide Compounds as STING Agonists

A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2a, R3, R3a, R4, R5, R5a, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds (I).

Methods of Synthesizing Substituted Purine Compounds

The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure. 2. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at about 16.5 claim 1 , 20.5 claim 1 , and 5.2° 2θ using Cu Kα radiation.3. The crystalline form of claim 2 , characterized by an XRPD pattern comprising peaks at about 16.5 claim 2 , 20.5 claim 2 , 5.2 claim 2 , and 14.2° 2θ using Cu Kα radiation.4. The crystalline form of claim 3 , characterized by an XRPD pattern comprising peaks at about 16.5 claim 3 , 20.5 claim 3 , 5.2 claim 3 , 14.2 claim 3 , 18.0 claim 3 , and 10.4° 2θ using Cu Kα radiation.5. The crystalline form of claim 1 , characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about 16.5 claim 1 , 20.5 claim 1 , 5.2 claim 1 , 14.2 claim 1 , 18.0 claim 1 , 10.4 claim 1 , 12.3 claim 1 , 10.0 claim 1 , 22.7 claim 1 , and 20.9° 2θ using Cu Kα radiation.612-. (canceled)13. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at about 5.5 claim 1 , 16.9 claim 1 , and 16.6° 2θ using Cu Ku radiation.14. The crystalline form of ...

Substituted nucleosides, nucleotides and analogs thereof

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

LABELLED NUCLEOTIDES

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a Csubstituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a Csubstituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside). 1. (canceled)2. (canceled)4. The oligonucleotide of claim 3 , wherein R is not present.6. The oligonucleotide of claim 5 , wherein the dotted line connecting the Fluor and the benzene ring comprises one or more spacer units such that the Fluor is held a sufficient distance from the nucleobase so as not to interfere with any interaction between the nucleotide and an enzyme.7. The oligonucleotide of claim 6 , wherein the spacer unit comprises —O— claim 6 , —NH— claim 6 , or —N(alkyl)-.9. The oligonucleotide of claim 8 , wherein the Fluor comprises a cyanine claim 8 , a rhodamine claim 8 , or a coumarin dye.10. The oligonucleotide of claim 9 , wherein the Fluor is a rhodamine dye.11. The oligonucleotide of claim 9 , wherein the Fluor is a Cy5 dye.12. The oligonucleotide of claim 9 , wherein the Fluor is attached to the Linker by reacting an N-hydroxysuccinimide ester of the Fluor with an amino moiety of the Linker.17. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with an aqueous solution comprising ethylenediaminetetraacetic acid (EDTA).18. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with a mutant polymerase.19. The oligonucleotide of claim 8 , wherein the oligonucleotide is in contact with a water soluble phosphine.20. The oligonucleotide of claim 8 , wherein the oligonucleotide is hybridized to a target polynucleotide claim 8 , and wherein the ...

Labelled nucleotides

The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a C 1-10 substituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a C 1-10 substituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside).

Beta-D-2'-DEOXY-2'-Alpha-FLUORO-2'-Beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.

SALT OF (SS)-ADENOSYL METHIONINE WITH INOSITOL HEXAPHOSPHATE, AND PROCESS FOR THE PREPARATION THEREOF

The invention relates to the salt of (SS)-adenosyl methionine with myo-inositol 1,2,3,4,5,6 hexakisphosphate, and pharmaceutical, nutraceutical or veterinary formulations containing it. 1. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate wherein the molar ratio of SAMe to inositol-hexaphosphate ranges from 0.75 to 1.0.2. (SS)—S-Adenosyl-L-methionine inositol-hexaphosphate according to wherein the ratio of SAMe to inositol hexaphosphate is equimolar.3. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to or having a SAMe ion content exceeding 30% by weight.4. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to having a SAMe ion content ranging from 30% to 40% by weight.5. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to having a SAMe ion content ranging from 34% to 39%.6. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to claim 1 , having isomeric purity exceeding 70%.7. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to claim 1 , having isomeric purity exceeding 95%.8. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to characterized in that it is substantially free from inorganic cations and inorganic or organic anions.9. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to claim 8 , characterised in that it is substantially free from alkali and alkaline-earth metals claim 8 , iron claim 8 , sulphates claim 8 , p-toluenesulphonates claim 8 , phosphates claim 8 , chlorides and 1 claim 8 ,4-butanedisulphates.10. (SS)—S-Adenosyl-L-methionine inositol hexaphosphate according to wherein the content of inositol pentaphosphate or other inositol-phosphates (1 to 4 phosphates) is globally lower than 5% by weight of the compound.11. A process for the preparation of (SS)—S-adenosyl-L-methionine inositol-hexaphosphate of claim 1 , comprising:a) production of SAMe from a microbial biomass, preferably a yeast,b) lysis of said biomass under acidic conditions,c) separation of the ...

FLUORESCENT POLYMERASE ENZYME SUBSTRATES HAVING PROTEIN SHIELDS

Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties. 1. A polymerase enzyme substrate comprising:a protein comprising at least 60 amino acids;a nucleotide component comprising at least one nucleoside polyphosphate attached through its phosphate portion to a first position on the protein;a dye component comprising at least one fluorescent dye moiety attached to a second position on the protein.2. The polymerase enzyme substrate of wherein the substrate is connected through covalent attachments.3. The polymerase enzyme substrate of wherein the protein comprises 60 to 1 claim 1 ,000 amino acids.4. The polymerase enzyme substrate of wherein the protein comprises 80 to 600 amino acids.5. The polymerase enzyme substrate of wherein the nucleotide component and dye component are covalently attached to the protein.6. The polymerase enzyme substrate of wherein the nucleotide component comprises two or more nucleoside phosphates.7. The polymerase enzyme substrate of wherein the substrate has 2 claim 1 , 3 claim 1 , 4 claim 1 , 5. 6 claim 1 , 7 claim 1 , or 8 nucleotide phosphates.8. The polymerase enzyme substrate of wherein the dye component comprises two or more fluorescent dye moieties.9. The polymerase enzyme substrate of wherein ...

Cyclic Di-Nucleotide Compounds as STING Agonists

A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R, R1a, R2a, R3, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds. (I) 13. A pharmaceutical composition , said pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) a compound according to or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof; and'}(b) a pharmaceutically acceptable carrier.14. A method of inducing an immune response in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.15. A method of inducing an immune response in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.16. A method of inducing a STING-dependent type I interferon production in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.17. A method of inducing a STING-dependent type I interferon production in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.18. A method of treating a cell proliferation disorder in a subject claim 1 , said method comprising administering a therapeutically effective amount of a compound according to to the subject.19. The method of claim 18 , wherein the cell proliferation disorder is cancer.20. A method of treating a cell proliferation disorder in a subject claim 13 , said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to to the subject.21. The method of ...

ANTI-HEPATITIS B VIRUS AGENT

The present disclosure aims to provide an anti-hepatitis B virus agent, and a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising a nucleic acid analogue as an active ingredient. 3. The method according to claim 2 , wherein the hepatitis B virus-related disease is one or more diseases selected from the group consisting of hepatitis B claim 2 , type-B liver cirrhosis claim 2 , and type-B liver cancer.56-. (canceled) The present disclosure relates to an anti-hepatitis B virus agent, and a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising a nucleic acid analogue as an active ingredient.As an active ingredient of an anti-hepatoma virus agent and a prophylactic or therapeutic agent for a hepatoma virus-related disease, a nucleic acid analog represented by the following formula:wherein Z is fluorine or hydrogen is known (Patent Literature 1).The present disclosure aims to provide an anti-hepatitis B virus agent, and a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising a nucleic acid analogue as an active ingredient.The present disclosure includes the following embodiments.An anti-hepatitis B virus agent comprising, as an active ingredient, a compound represented by the following formula (1):wherein R is a halogen atom, an amino group, a methoxy group, or a cyano group, or its prodrug, or a pharmaceutically acceptable salt thereof, or a solvate thereof.The present disclosure provides an anti-hepatitis B virus agent, and a prophylactic or therapeutic agent for a hepatitis B virus-related disease, each comprising a nucleic acid analogue as an active ingredient.The above summary of the present disclosure is not intended to describe each disclosed embodiment or every implementation of the present disclosure.The description of the present disclosure that follows more specifically provides examples of illustrative embodiments.In several places throughout the ...

PROCESS FOR PREPARING NUCLEOSIDE PRODRUGS

A process for preparing phosphoramidates of nucleosides where a desired enantiomer, having regard to the asymmetric chiral center of the phosphorus atom P, is provided in an enriched amount. The process comprises admixing a nucleoside with a phosphorochloridate in the presence of a catalyst comprising a metal salt selected from the group consisting of salts of Cu, Fe, La and Yb. 137-. (canceled)39. The method of treatment of claim 38 , wherein the composition further comprises a pharmaceutically acceptable carrier claim 38 , diluent or excipient.40. The method of treatment of claim 38 , wherein the cancer is breast cancer.41. The method of treatment of claim 38 , wherein the cancer is colon cancer.42. The method of treatment of claim 38 , wherein the cancer is prostate cancer.43. The method of treatment of claim 38 , wherein the cancer is leukemia.44. The method of treatment of claim 38 , wherein the composition is administered orally.45. The method of treatment of claim 38 , wherein the composition is administered parenterally.46. The method of treatment of claim 45 , wherein the composition is administered intravenously.47. The method of treatment of claim 38 , wherein the composition is administered topically. The present invention relates to a process for preparing chemical compounds and to the chemical compounds prepared by the present process.The chemical synthesis of a chiral compound usually results in a racemic mixture of the compound in which R and S enantiomers are present in equal amounts.Many biologically active systems, however, involve specific enantiomers or diastereoisomers of chiral compounds. Such chiral biological systems may react differently to the different enantiomers or diasteroisomers of a pharmaceutical chiral compound.Administering to a patient a racemic mixture of a chiral pharmaceutical compound may mean that only one enantiomer of the compound can partake in the desired therapeutic reaction. The synthesis of a chiral pharmaceutical ...

MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS

2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions. 113-. (canceled)15. The method of claim 14 , wherein X is O claim 14 , and each Yis H.16. The method of claim 14 , wherein the Flaviviridae virus is hepatitis C virus.17. The method of claim 16 , wherein the second anti-viral agent is an interferon claim 16 , a ribavirin claim 16 , or a combination thereof.18. The method of claim 14 , wherein the second antiviral agent is ribavirin.19. The method of claim 17 , wherein the second antiviral agent is pegylated interferon alpha 2a.20. The method of claim 19 , further comprising administering ribavirin to the host.21. The method of claim 15 , wherein Ris monophosphate claim 15 , diphosphate claim 15 , triphosphate claim 15 , a stabilized phosphate; and Ris H.22. The method of claim 21 , wherein Base* is uracil.23. The method of claim 21 , wherein the second antiviral agent is an interferon claim 21 , a ribavirin claim 21 , or a combination thereof.24. The method of claim 23 , wherein the second antiviral agent is ribavirin.25. The method of claim 23 , further comprising administering pegylated interferon alpha 2a to the host.26. The method of claim 14 , wherein X is O claim 14 , each Yis H; Ris H and Ris monophosphate claim 14 , diphosphate claim 14 , triphosphate claim 14 , or a stabilized phosphate.27. ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

Compounds

Disclosed herein are 2′-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

PROCESS OF MAKING REGADENOSON AND NOVEL POLYMORPHS THEREOF

Novel processes for making the N-pyrrazole substituted 2-adenosine derivative regadenoson and a novel polymorph thereof. The novel polymorph of regadenoson designated form H and drug substances and pharmaceutical compositions including the novel polymorph H are disclosed. 14.-. (canceled)6. (canceled)7. The process according to wherein the distillation is conducted at a temperature in the range of 80-120° C.89.-. (canceled)10. A polymorphic form of regadenoson characterized bya powder X-ray diffraction powder x-ray diffraction (XRPD) spectrum comprising at least one peak at the following °2θ angles (±0.2): 6.16, 10.31, 10.72 and/or 25.52±0.2 (°2θ) measured with a Cu-Kα irradiation; anda differential scanning calorimetry (DSC) peak in the range of 265-280° C. measured with a heating rate of 10° C.11. The polymorphic form of regadenoson according to comprising a characteristic XRPD peak at 25.52±0.2 (°2θ).12. The polymorphic form of regadenoson according to comprising a characteristic XRPD peak at 6.16±0.2 (°2θ)13. The polymorphic form of regadenoson according to comprising a characteristic XRPD peak at 10.31±0.2 (°2θ).14. The polymorphic form of regadenoson according to comprising characteristic XRPD peaks at 6.16 and 25.52±0.2 (°2θ).15. The polymorphic form of regadenoson according to comprising characteristic XRPD peaks at 6.16 claim 10 , 10.31 claim 10 , 10.72 and 25.52±0.2 (°2θ).16. The polymorphic form of regadenoson according to characterized by a powder X-ray diffractogram comprising peaks at one or more of 6.16 claim 10 , 10.31 claim 10 , 10.72 claim 10 , 12.38 claim 10 , 16.37 claim 10 , 21.57 claim 10 , 22.59 claim 10 , 25.52 claim 10 , 26.28 claim 10 , and 27.76±0.2 (°2θ) claim 10 , measured with a Cu-Kα irradiation.17. A regadenoson drug substance comprising at least about 5% of the polymorphic form of regadenoson according to .18. A regadenoson drug substance comprising at least about 50% of the polymorphic form of regadenoson according to .19. A ...

ADENOSINE ANALOGS AS METHYLTRANSFERASE INHIBITORS FOR TREATING CANCER

Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structures 122-. (canceled)24. The pharmaceutical composition of wherein Y is N.25. The pharmaceutical composition of wherein A is —CH—.26. The pharmaceutical composition of wherein Ris phenyl.27. The pharmaceutical composition of wherein t is 1.31. The pharmaceutical composition of of formula Ia wherein{'sup': 3', '6', '7, 'sub': 2', 'm', '1', '3, 'Ris —((CH))phenyl substituted with one to three substituents chosen independently from —O((C-C)alkyl), —O((CH)RR), and halogen.'}328. The pharmaceutical composition of claim comprising a compound of Formula Ia wherein{'sup': 3', '6', '7, 'sub': 2', 'm', '1', '3', '1', '20', '2', 'm, 'Ris —((CH))heteroaryl optionally substituted with one to four substituents chosen independently from —O((C-C)alkyl), —O((CH)RR) and (C-C)hydrocarbon, wherein said —((CH))heteroaryl is a nitrogen heteroaryl.'}37. The pharmaceutical composition of comprising a compound of Formula IIa wherein{'sup': 4', '6', '7, 'sub': 2', 'm', '2', 'm', '1', '3', '1', '20, 'Ris chosen from —OH and —NH((CH))phenyl, said —NH((CH))phenyl optionally substituted with one to three substituents chosen independently from halogen, —O((C-C)alkyl), —O((CH)RR), and (C-C)hydrocarbon.'}42. A method of inhibiting the activity of a methyltransferase enzyme comprising contacting methyltransferase enzyme with a pharmaceutical composition according to . This application claims the benefit of priority to U.S. provisional application No. 62/396,318, filed on Sep. 19, 2016, the disclosure of which is hereby incorporated herein in its entirety.This invention was made with government support under GM396056 awarded by the National Institutes of Health. The government has certain rights in the invention.This invention relates to chemical compounds having methyltransferase inhibitory activity and their use in the treatment of diseases and conditions associated with inappropriate ...

MODIFIED NUCLEOTIDES

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3′-OH blocking group covalently attached thereto, such that the 3′ carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R′)2-O—R″, —C(R′)2-N(R″)2, —C(R′)2-N(H)R″, —C(R′)2-S—R″ and —C(R′)2-F, wherein each R″ is or is part of a removable protecting group; each R′ is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R′)2 represents an alkylidene group of formula=C(R′″)2 wherein each R′″ may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R″ is exchanged for H or, where Z is —C(R′)2-F, the F is exchanged for OH, SH or NH2, preferably OH, which intermediate dissociates under aqueous conditions to afford a molecule with a free 3′OH; with the proviso that where Z is —C(R′)2-S—R″, both R′ groups are not H. 1. (canceled)2. (canceled)3. A modified nucleoside triphosphate molecule comprising a base and a deoxyribose sugar moiety , wherein the 3′ carbon atom of the sugar moiety has covalently attached thereto a group of the structure:{'br': None, '—O—Z'}wherein Z is a removable protecting group comprising an azido group.4. The molecule of claim 3 , wherein the removable protecting group is azidomethyl.5. The molecule of claim 4 , wherein the base is a purine claim 4 , a pyrimidine or a deazapurine.6. The molecule of claim 4 , wherein the base is adenine claim 4 , 7-deazaadenine claim 4 , guanine claim 4 , or 7-deazaguanine.7. The molecule of claim 4 , wherein the base is cytosine claim 4 , thymine or uracil.8. The molecule of claim 4 , wherein the base is linked ...

METHODS OF MYOCARDIAL PERFUSION IMAGING

The present invention provides a method of myocardial perfusion imaging using reduced doses of (1-{9-[(4S,2R,3R,5R)3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide. 114-. (canceled)16. The method of claim 15 , wherein the dose of the compound is 30 μg/kg.17. The method of claim 15 , wherein the step of administering the pharmaceutically effective amount of the compound takes place by infusion of a pharmaceutically acceptable composition thereof.18. The method of claim 15 , wherein the step of administering the pharmaceutically effective amount of the compound takes place by a bolus injection of a pharmaceutically acceptable composition thereof. This application is a continuation of U.S. patent application Ser. No. 13/525,223, filed Jun. 15, 2012, now U.S. Pat. No. 8,536,150, which is a continuation of U.S. patent application Ser. No. 13/286,069, filed Oct. 31, 2011, now abandoned, which is a continuation of U.S. patent application Ser. No. 12/435,176, filed May 4, 2009, now U.S. Pat. No. 8,071,566, which is a continuation of U.S. patent application Ser. No. 11/070,768, filed Mar. 2, 2005, now U.S. Pat. No. 7,582,617, which is a continuation of U.S. patent application Ser. No. 10/614,702, filed Jul. 3, 2003, now abandoned, which is a continuation of U.S. patent application Ser. No. 09/792,617, filed Feb. 23, 2001, now abandoned, which claims the benefit of the filing dates of Provisional Patent Application Ser. Nos. 60/219,876, filed Jul. 21, 2000 and 60/184,296, filed Feb. 23, 2000, the specifications of each of which are incorporated herein by reference.This invention relates to a method of identifying compounds that are selective partial A-adenosine receptor agonists, preferably with a short duration of action. Such compounds provide coronary dilation in mammals without causing corresponding significant peripheral vasodilation. The invention also relates to a method of using such compounds as adjuncts in cardiac ...

METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS

The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning calorimetry profile, as well as a unique crystalline structure. 2. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at about 16.5 claim 1 , 20.5 claim 1 , and 5.2° 2θ using Cu Kα radiation.3. The crystalline form of claim 2 , characterized by an XRPD pattern comprising peaks at about 16.5 claim 2 , 20.5 claim 2 , 5.2 claim 2 , and 14.2° 2θ using Cu Kα radiation.4. The crystalline form of claim 3 , characterized by an XRPD pattern comprising peaks at about 16.5 claim 3 , 20.5 claim 3 , 5.2 claim 3 , 14.2 claim 3 , 18.0 claim 3 , and 10.4° 2θ using Cu Kα radiation.5. The crystalline form of claim 1 , characterized by an XRPD pattern comprising at least three peaks selected from the group consisting of about 16.5 claim 1 , 20.5 claim 1 , 5.2 claim 1 , 14.2 claim 1 , 18.0 claim 1 , 10.4 claim 1 , 12.3 claim 1 , 10.0 claim 1 , 22.7 claim 1 , and 20.9° 2θ using Cu Kα radiation.6. The crystalline form of claim 1 , characterized by an XRPD pattern comprising at least four peaks selected from the group consisting of about 16.5 claim 1 , 20.5 claim 1 , 5.2 claim 1 , 14.2 claim 1 , 18.0 ...

Adenosine receptor activation reagent and the uses of thereof

The present invention relates to application of N(6)-(2-hydroxyethyl)-adenosine (HEA) and its derivatives as an adenosine Areceptor agonist in preparation of drug or food, the HEA and its derivatives are used in treatment of diseases relating to adenosine receptor regulator, such as insomnia, pain, convulsion, apoplexia, Parkinson's disease, opioid drug addiction and kidney ischemia reperfusion injury etc. The present invention provides a new method for treatment of the diseases relating to nervous system and kidney. 1. An adenosine receptor agonist , wherein the agonist includes N(6)-(2-hydroxyethyl) adenosine (HEA) or its derivatives.2. The agonist according to claim 1 , wherein said adenosine receptor is one or more of A claim 1 , A claim 1 , A claim 1 , A.3. The agonist according to claim 1 , wherein the adenosine receptor is Areceptor.6. The agonist according to claim 5 , wherein R1 is C(CH)CHOH claim 5 , CH(CH)CHOH or C(CH).7. A method for treating or preventing convulsion claim 5 , pain claim 5 , insomnia claim 5 , apoplexia claim 5 , Parkinson's disease or opioid drug addiction claim 5 , renal failure or renal ischemia reperfusion injury comprising using HEA or its derivatives.9. The method according to claim 7 , wherein R1 is C(CH)CHOH claim 7 , CH(CH)CHOH or C(CH).10Cordyceps, Cordyceps militaris, Paecilomyces cicadae. The method according to claim 7 , wherein said HEA is selected from the group consisting of fungus and culture extract of the fungus.11Cordyceps cicadae, Cordyceps militaris, Cordyceps sinensis. The method according to claim 7 , wherein said HEA is selected from the group consisting of and extract of its artificial culture.12. The method according to claim 7 , wherein said HEA treats or prevents convulsion claim 7 , pain claim 7 , insomnia claim 7 , apoplexia claim 7 , Parkinson's disease claim 7 , or opioid drug addiction via the adenosine receptor.13. The method according to claim 12 , wherein said adenosine receptor is the Areceptor. The ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs. 2. The compound of claim 1 , wherein Ris halo.3. The compound of claim 1 , wherein Ris —OR.4. The compound of claim 3 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris Nor NH.6. The compound of claim 1 , wherein Ris an optionally substituted Calkyl.7. The compound of claim 1 , wherein both - - - - - - are each absent.8. The compound of claim 7 , wherein Ris —OH.9. The compound of claim 7 , wherein Ris hydrogen.11. The compound of claim 10 , wherein Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative; and Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative.15. The compound of claim 10 , wherein Ris an optionally substituted N-linked amino acid or is an optionally substituted N-linked amino acid ester derivative; and Ris an —O-optionally substituted aryl claim 10 , an —O-optionally substituted heteroaryl or an —O-optionally substituted heterocyclyl.17. The compound of claim 10 , wherein Zis O.18. The compound of claim 1 , wherein both - - - - - - are each a single bond.19. The compound of claim 18 , wherein Ris an —O-optionally substituted Calkyl.20. (canceled)22. (canceled)24. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , excipient or combination thereof.25. A method of ameliorating or treating a HCV infection comprising administering to a subject suffering from the HCV infection an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.26. A method for inhibiting replication of a hepatitis C virus comprising contacting a cell ...

STABLE SOLID FORMS OF REGADENOSON

A process for the preparation of the amorphous form of Regadenoson of formula 2. The process according to claim 1 , wherein in step a) said C-Calcohol is ethanol.3. The process according to claim 2 , wherein said ethanol is dry.4. The process according to claim 1 , wherein in step a) said methylamine is in a concentration of between 10 and 40%.5. The process according to claim 1 , wherein in step a) said 2-(4-ethoxycarbonylpyrazol-1-yl)adenosine is in a molar concentration of between 0.5 and 0.1 M.6. The process according to claim 1 , wherein in step b) the reaction temperature is comprised between 80-85° C. claim 1 , the pressure is about 3 bar claim 1 , and the reaction time is about 30 hours.7. The process according to claim 2 , wherein step c) is carried out by removing methylamine by distillation under vacuum at 40° C. claim 2 , step d) is carried out by cooling the reaction mixture at 20-25° C. claim 2 , step e) is carried out by diluting the reaction mixture 1:1 with anhydrous ethanol and maintaining the reaction mixture under stirring for 30-60 minutes at 20-25° C.8. A Regadenoson solvate with one molecule of trifluoroethanol (Form E) claim 2 , comprising the following diagnostic peaks of X-ray diffraction spectrum in 2-theta (θ) values: 4.98 claim 2 , 12.08 claim 2 , 14.66 claim 2 , 17.60 claim 2 , 17.96 claim 2 , 19.20 claim 2 , 19.62 claim 2 , 20.24 claim 2 , 20.78 claim 2 , 21.08 claim 2 , 21.52 claim 2 , 23.18 claim 2 , 24.10 24.24 claim 2 , 25.08 claim 2 , 25.52 claim 2 , 26.02 claim 2 , 26.64 claim 2 , 27.36 claim 2 , 27.66 claim 2 , 27.84 claim 2 , and 28.74.9. A process for the preparation of the Regadenoson solvate of claim 8 , comprising:a. treating amorphous Regadenoson in dry trifluoroethanol, at a temperature comprised between 15-50° C. for 0.5-1.0 hour to provide a reaction mixture;b. filtering said reaction mixture, recovering a filtrate;c. concentrating said filtrate concentrated under vacuum, to provide a residue; andd. maintaining said ...

METHODS FOR PREPARING DEUTERATED 1,2,3-TRIAZOLES

This disclosure relates to a method that involves reacting an azide with an alkyne in the presence of deuterated water and a copper-containing catalyst, thereby forming a deuterated 1,2,3-triazole. 1. A method , comprising:reacting an azide with an alkyne in the presence of deuterated water and a copper-containing catalyst, thereby forming a deuterated 1,2,3-triazole.2. The method of claim 1 , wherein the 1 claim 1 ,2 claim 1 ,3-triazole contains a deuterium atom at the 5 position.3. The method of claim 1 , wherein the alkyne is ethyne substituted with a substituent comprising C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , C-Cheterocycloalkyl claim 1 , C-Cheterocycloalkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , C-Calkylsilyl claim 1 , C-Calkylstannyl claim 1 , or a boronic acid group or an ester thereof.4. The method of claim 3 , wherein the substituent comprises C-Calkyl claim 3 , C-Cheterocycloalkyl claim 3 , aryl claim 3 , or heteroaryl claim 3 , which is optionally substituted with D claim 3 , halo claim 3 , CN claim 3 , OR claim 3 , SR claim 3 , N(R) claim 3 , C-Calkyl or C-Cheterocycloalkyl claim 3 , R being H claim 3 , C-Calkyl claim 3 , C-Calkenyl claim 3 , C-Calkynyl claim 3 , C-Ccycloalkyl claim 3 , C-Ccycloalkenyl claim 3 , C-Cheterocycloalkyl claim 3 , C-Cheterocycloalkenyl claim 3 , aryl claim 3 , or heteroaryl.6. The method of claim 1 , wherein the azide comprises C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Ccycloalkyl claim 1 , C-Ccycloalkenyl claim 1 , C-Cheterocycloalkyl claim 1 , C-Cheterocycloalkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , a nucleoside group claim 1 , or a deoxynucleoside group.7. The method of claim 6 , wherein the azide comprises aryl claim 6 , a nucleoside group claim 6 , or a deoxynucleoside group claim 6 , which is optionally substituted with D claim 6 , halo claim 6 , CN claim 6 , OR claim 6 , SR claim 6 , N(R) claim 6 , C-Calkyl ...

PROCESS FOR PREPARING 3'-O-AMINO-RIBONUCLEOTIDE

The invention relates to a process for preparing a 3′-O-amino-ribonucleotide. It also relates to a compound of formula (III), and its use as a precursor for the synthesis of a 3′-O-amino-ribonucleotide. 2. The process according to claim 1 , wherein B is a nitrogenous base selected from the group consisting of adenine claim 1 , guanine claim 1 , cytosine claim 1 , thymine claim 1 , uracil claim 1 , and a protected derivative thereof.3. The process according to claim 1 , wherein the sulfonyl group(s) are selected from the group consisting of tosyl claim 1 , mesyl claim 1 , trifluoromethanesulfonyl group claim 1 , and any combination thereof.4. The process according to claim 1 , wherein the source of sulfonyl group(s) comprises tosyl chloride.5. The process according to claim 1 , wherein the source of sulfonyl group(s) comprises trifluoromethanesulfonyl chloride and/or trifluoromethanesulfonic anhydride.6. The process according to claim 1 , wherein G and G′ are identical or different claim 1 , and are represent a protecting group selected from the group consisting of tert-butyldimethylsilyl (TBS) claim 1 , monomethoxytrityl (MMTr) claim 1 , dimethoxytrityl (DMTr) claim 1 , (triisopropyl-siloxy)methyl (TOM) claim 1 , and triisopropylsilyl (TIPS).9. The process according to claim 8 , wherein step (B) comprises the substeps:(B-1) oxidizing the 3′-hydroxy group of the compound of formula (I.2) into a ketone group, by means of an oxidizing agent; and(B-2) reducing the ketone group of the compound obtained in step (B-1), by means of a hydride source, to obtain the compound of formula (I).13. (canceled)14. (canceled)15. The process according to claim 1 , wherein the source of sulfonyl group(s) comprises trifluoromethanesulfonic anhydride.16. The process according to claim 9 , wherein:the oxidizing agent is selected from the group consisting of: Dess-Martin periodinane and pyridinium dichromate, andthe hydride source is sodium borohydride.17. The compound according to claim 11 ...

Substituted nucleosides, nucleotides and analogs thereof

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS

2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions. 2. A compound of claim 1 , wherein B is a 3-7 membered carbocyclic ring.3. A compound of claim 1 , wherein B is a 3-7 membered heterocyclic ring having one or more O claim 1 , S and/or N atoms.4. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.5. A method for the treatment of a host infected with a hepatitis C virus claim 1 , comprising administering an effective treatment amount of a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.6. The method of claim 5 , wherein the compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with a second anti-viral agent.7. The method of claim 6 , wherein the second anti-viral agent is selected from the group consisting of an interferon claim 6 , a ribavirin claim 6 , an interleukin claim 6 , a NS3 protease inhibitor claim 6 , a cysteine protease inhibitor claim 6 , a phenan-threnequinone claim 6 , a thiazolidine derivative claim 6 , a thiazolidine claim 6 , a benzanilide claim 6 , a phenan-threnequinone claim 6 , a helicase inhibitor claim 6 , a polymerase inhibitor claim 6 , a nucleotide analogue claim 6 , a gliotoxin claim 6 , a cerulenin claim 6 , an antisense phosphorothioate ...

MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS

2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions. 118-. (canceled)20. The method of claim 19 , wherein Ris H claim 19 , monophosphate claim 19 , diphosphate claim 19 , triphosphate claim 19 , or a stabilized phosphate prodrug.21. The method of claim 19 , wherein Ris acyl; lower acyl; alkyl; lower alkyl; sulfonate ester; alkyl or arylalkyl sulfonyl; methanesulfonyl; benzylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo provides a compound wherein Ris H.22. The method of claim 19 , wherein each Yis H.23. The method of claim 19 , wherein Base is selected from the group consisting of cytosine claim 19 , thymine claim 19 , uracil claim 19 , pyrrolopyrimidine and pyrazolopyrimidine.24. The method of claim 19 , wherein Base is cytosine.25. The method of claim 19 , wherein Base is uracil.26. The method of claim 19 , wherein the compound claim 19 , or a pharmaceutically acceptable salt thereof claim 19 , is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.27. The method of claim 26 , wherein the pharmaceutical composition is in the form of an oral dosage.28. The method of claim 27 , wherein the oral dosage comprises from 50 to 1000 mg of ...

Modified nucleotides

The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3′-OH blocking group covalently attached thereto, such that the 3′ carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R′)2-O—R″, —C(R′)2-N(R″)2, —C(R′)2-N(H)R″, —C(R′)2-S—R″ and —C(R′)2-F, wherein each R″ is or is part of a removable protecting group; each R′ is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R′)2 represents an alkylidene group of formula ═C(R′″)2 wherein each R′″ may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R″ is exchanged for H or, where Z is —C(R′)2-F, the F is exchanged for OH, SH or NH2, preferably OH, which intermediate dissociates under aqueous conditions to afford a molecule with a free 3′OH; with the proviso that where Z is —C(R′)2-S—R″, both R′ groups are not H.

Phosphoramidate nucleoside prodrug for treating viral diseases and cancer, processes for their preparation and their use

The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. 3. The phosphoramidate nucleoside prodrug of selected from the group consisting of: allyl (S)-2-{(S)-[(R)-1-methyl-2-(6-amino-9H-purin-9-yl)-ethoxy]-phenoxy-phosphorylamino}-propanoate (1.1(1)) claim 1 , 2-methoxy-ethyl (S)-2-{(S)-[(R)-1-methyl-2-(6-amino-9H-purin-9-yl)-ethoxy]-phenoxy-phosphorylamino}-propanoate (1.1(2)) claim 1 , (S)-1-ethoxycarbonyl-ethyl (S)-2-{[(2R claim 1 ,3R claim 1 ,4R claim 1 ,5R)-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propanoate (1.2(1)) claim 1 , (S)-1-isopropyloxycarbonyl-ethyl (S)-2-{[(2R claim 1 ,3R claim 1 ,4R claim 1 ,5R)-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propanoate (1.2(2)) claim 1 , (S)-1-benzyloxycarbonyl-ethyl (S)-2-{[(2R claim 1 ,3R claim 1 ,4R claim 1 ,5R)-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propanoate (1.2(3)) claim 1 , (S)-1-cyclopropoxycarbonyl-ethyl (S)-2-{[(2R claim 1 ,3R claim 1 ,4R claim 1 ,5R)-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propanoate (1.2(4)) claim 1 , isopropyl (S)-2-((S)-2-{[(2R claim 1 ,3R claim 1 ,4R claim 1 ,5R)-5-(2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionylamino)-propanoate (1.2(5)) claim 1 , (S)-1-carboxy-ethyl (S)-2 ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 4. The pharmaceutical composition of claim 1 , in a dosage form.5. The pharmaceutical composition of claim 4 , in an oral dosage form.6. The pharmaceutical composition of claim 5 , in a tablet.7. The pharmaceutical composition of claim 5 , in a capsule.8. The pharmaceutical composition of claim 2 , in a dosage form.9. The pharmaceutical composition of claim 8 , in an oral dosage form.10. The pharmaceutical composition of claim 9 , in a tablet.11. The pharmaceutical composition of claim 9 , in a capsule.12. The pharmaceutical composition of claim 3 , in a dosage form.13. The pharmaceutical composition of claim 12 , in an oral dosage form.14. The pharmaceutical composition of claim 13 , in a tablet.15. The pharmaceutical composition of claim 13 , in a capsule.19. The pharmaceutical composition of claim 16 , in a dosage form.20. The pharmaceutical composition of claim 20 , in an oral dosage form.21. The pharmaceutical composition of claim 21 , in a tablet.22. The pharmaceutical composition of claim 21 , in a capsule.23. The pharmaceutical composition of claim 17 , in a dosage form.24. The pharmaceutical composition of claim 23 , in an oral dosage form.25. The pharmaceutical composition of claim 24 , in a tablet.26. The pharmaceutical composition of claim 24 , in a capsule.27. The pharmaceutical composition of claim 18 , in a dosage form.28. The pharmaceutical composition of claim 27 , in an oral dosage form.29. The pharmaceutical composition of claim 28 , in a tablet.30. The pharmaceutical composition of claim 28 , in a capsule. This application is a continuation of U.S. Ser. No. 15/063,461 filed on Mar. 7, 2016 and claims priority to U.S. Ser. No. 62/129,319 filed on Mar. 6, 2015; U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015; and, U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof ...

BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'BETA-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT

A compound of the structure: 2. The compound of claim 1 , wherein the stabilized phosphate prodrug is a phosphoramidate.4. The compound of claim 3 , wherein Ris aryl.5. The compound of claim 4 , wherein Ris phenyl.6. The compound of claim 3 ,wherein{'sup': '16', 'Ris hydrogen;'}{'sup': '17', 'sub': 1', '8, 'Ris (C-C)alkyl;'}{'sup': '18', 'Ris hydrogen; and'}{'sup': '19', 'sub': 1', '6, 'Ris (C-C)alkyl.'}7. The compound of claim 6 , wherein Ris aryl.8. The compound of claim 7 , wherein Ris phenyl. This application is a continuation of U.S. Ser. No. 15/063,461 filed on Mar. 7. 2016 and claims priority to U.S. Ser. No. 62/129,319 filed on March 6, 2015, U.S. Ser. No. 62/253,958 filed on Nov. 11, 2015, and U.S. Ser. No. 62/276,597 filed on Jan. 8, 2016. Each of these references is incorporated herewith in their entirety.The present invention is directed to nucleotide compounds and compositions and uses thereof to treat the Hepatitis C virus (“HCV”).Hepatitis C (HCV) is an RNA single stranded virus and member of the genus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left to progress, liver failure which may require a liver transplant, Approximately 170-200 million people worldwide are infected, with an estimated 3-4 million infections in the United States.RNA polymerase is a key component in the targeting of RNA single stranded viruses. The HCV non-structural protein NS5B RNA-dependent RNA polymerase is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. As a result, HCV NS5B is an attractive target for the current drug discovery and development of anti-HCV agents. There are two major subclasses of NS5B inhibitors: nucleoside analogs, which are anabolized to their active triphosphates—which act as alternative substrates for the polymerase—and non-nucleoside inhibitors (NNIs), which bind to allosteric regions on the protein. Nucleoside or nucleotide ...

DOT1L DEGRADERS AND USES THEREOF

Provided herein are bifunctional compounds with a moiety or domain that is a binder of the ubiquitin receptor RPN13 and another moiety or domain that is a binder of a target protein DOT1L to induce degradation of DOT1L. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers). Provided also are methods of inducing the degradation of DOT1L by administering a bifunctional compound or composition described herein, wherein one domain of the bifunctional compound is a binder of the ubiquitin receptor RPN13 and another domain of the compound is a binder of the target protein DOT1L in a subject. 3. The compound of claim 2 , wherein:{'sup': '1', '#text': 'for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is phenyl optionally substituted with R;'}for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is phenyl substituted with halogen;for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is phenyl substituted with two instances of halogen;for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is phenyl substituted with at least one Cl;{'sup': '1', '#text': 'for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is naphthyl optionally substituted with R;'}{'sup': '1', '#text': 'for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is a 5- or 6-membered monocyclic heteroaryl group, having 1-3 heteroatoms selected from the group consisting of O, N, and S, optionally substituted with R; or'}{'sup': '1', '#text': 'for each set of two moieties A bound to the same carbon atom, one A is hydrogen and the other A is an 8- to 10-membered bicyclic heteroaryl group containing 1-3 heteroatoms selected from the group ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs. 129.-. (canceled)31. The compound of claim 30 , wherein Ris an unsubstituted Calkyl.32. The compound of claim 30 , wherein Ris methyl.33. The compound of claim 30 , wherein Ris ethynyl.34. The compound of claim 30 , wherein Ris hydrogen.40. The compound of claim 39 , wherein Rand Rare each —O-isopropyl.42. The compound of claim 30 , wherein Ris ethyl. Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application, are hereby incorporated by reference under 37 CFR 1.57.The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled SEQLISTING 65.TXT, created Feb. 13, 2014, which is 1 Kb in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.The present application relates to the fields of chemistry, biochemistry and medicine. More particularly, disclosed herein are nucleotide analogs, pharmaceutical compositions that include one or more nucleotide analogs and methods of synthesizing the same. Also disclosed herein are methods of treating diseases and/or conditions with a nucleotide analog, alone or in combination therapy with one or more other agents.Nucleoside analogs are a class of compounds that have been shown to exert antiviral and anticancer activity both in vitro and in vivo, and thus, have been the subject of widespread research for the treatment of viral infections. Nucleoside analogs are usually therapeutically inactive compounds that are converted by host or viral enzymes to their respective active anti-metabolites, which, in turn, may inhibit polymerases involved in viral or cell proliferation. The activation occurs by a ...

Synthesis of Protected 3'-Amino Nucleoside Monomers

Orthogonally protected 3′-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3′-amino group in the presence of the unprotected nucleoside base. 132.-. (canceled)33. A synthetic preparation of a N3′→P5′ phosphoramidate or thiophosphoramidate oligonucleotide , comprising an oligonucleotide comprising a 3′-amino-3′-deoxy nucleoside monomer having a nucleoside base which is protected with a dialkyl- , di(cycloalkyl)- or di(aralkyl)-formamidinyl group.34. The synthetic preparation of claim 33 , wherein the 3′-amino nucleoside monomer is a guanosine or an adenosine monomer.35. The synthetic preparation of claim 33 , wherein the 3′-amino nucleoside monomer is a cytidine monomer.36. The synthetic preparation of claim 33 , wherein the 3′-amino nucleoside monomer is the 3′-terminal monomer.37. The synthetic preparation of claim 33 , wherein the oligonucleotide comprises a deprotected 3′-amino for addition of a further monomer to the growing oligonucleotide chain.38. The synthetic preparation of claim 33 , wherein the oligonucleotide is composed of 3′-amino-3′-deoxy nucleoside monomers independently selected from guanosine claim 33 , adenosine claim 33 , cytidine and thymidine claim 33 , wherein all of the guanosine claim 33 , adenosine and cytidine monomers have a nucleoside base which is protected with a dialkyl- claim 33 , di(cycloalkyl)- or di(aralkyl)-formamidinyl group and all of the thymidine monomers have a unprotected nucleoside base. This application claims priority to U.S. provisional application Ser. No. 60/585,193, filed on Jul. 2, 2004, which is hereby incorporated by reference in its entirety.The present invention relates to efficient methods of synthesis of orthogonally protected 3′-amino nucleoside monomers, useful for the synthetic preparation of oligonucleotide analogs, and to the orthogonally protected monomers prepared by such methods.Asai, A. et al., 63(14):3931-9 (2003). ...

MODIFIED OLIGONUCLEOTIDES AND METHODS FOR THEIR SYNTHESIS

Modified oligonucleotides that contain one or more of the phosphate groups substituted at phosphorus and methods for their synthesis are disclosed. 2. The compound of claim 1 , wherein Ris —NRR claim 1 , —OR claim 1 , and —SR.3. The compound of or claim 1 , wherein Ris —NRR.4. The compound of any preceding claim claim 1 , wherein Ris —H claim 1 , —NRRor —OR.5. The compound of any preceding claim claim 1 , wherein Ris NRR.6. The compound of any preceding claim claim 1 , wherein each R claim 1 , R claim 1 , Rand Ris independently selected from —H and —Calkyl optionally substituted with one or more substituents selected from —F claim 1 , —Cl claim 1 , —OH claim 1 , —Calkoxy claim 1 , —NH claim 1 , —NH(Calkyl) claim 1 , and —N(Calkyl).7. The compound of claim 6 , wherein R claim 6 , R claim 6 , R claim 6 , Rare each methyl.8. The compound of any one of to claim 6 , wherein Rand Rtogether form an alkylene or heteroalkylene chain of 2-4 atoms in length and Rand Rare each independently selected from —H and —Calkyl.9. The compound of claim 8 , wherein Rand Rtogether form —CH—CH— and Rand Rare each independently selected from —H and methyl.10. The compound of any one of to claim 8 , wherein Rand R claim 8 , together with the atom to which they are bound claim 8 , form a 5-8 membered heterocycle claim 8 , optionally a pyrrolidine.11. The compound of claim 10 , wherein Rand R claim 10 , together with the atom to which they are bound claim 10 , form a 5-8 membered heterocycle claim 10 , optionally a pyrrolidine.12. A method of synthesising a compound according to any one of to .13. A method of synthesising a compound according to any one of to claim 10 , the method comprising reaction of a phosphorous acid derivative with an imino derivative HN═CRRor an N-silylated derivative RSiN═CRRin the presence of an oxidant claim 10 , and optionally a silylating agent and/or a base.14. The method of claim 13 , wherein the phosphorous acid derivative is a phosphite or H-phosphonate.15. The ...

COMBINATION, KIT AND METHOD OF REDUCING INTRAOCULAR PRESSURE

The present invention is directed to a combination or a kit comprising a prostaglandin analog and an adenosine receptor Aagonist and to a method of reducing intraocular pressure (IOP) in a subject using such combination or kit. The invention is particularly directed to a combination of latanoprost marketed under the brand Xalatan™ and Compound A. 2. The combination of claim 1 , wherein the prostaglandin analog is selected from the group consisting of latanoprost claim 1 , travoprost claim 1 , unoprostone and bimatoprost.4. The combination of claim 1 , wherein the adenosine receptor Aagonist is Compound A claim 1 , ((2R claim 1 ,3S claim 1 ,4R claim 1 ,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3 claim 1 ,4-dihydroxytetrahydrofuran-2-yl)methyl nitrate or a pharmaceutically acceptable salt thereof.5. The combination of claim 1 , wherein the Aagonist is formulated for administration to an eye of the subject simultaneously claim 1 , separately or sequentially to the application of the prostaglandin analog to the eye of the subject.6. The combination of claim 1 , formulated for administration of about 0.05 mg/ml to about 7.0 mg/ml of the Aagonist with about 30 μg/ml to about 50 μg/ml of the prostaglandin analog to an eye of the subject.7. The combination of claim 6 , formulated for administration of about 20-700 μg of the Aagonist to an eye of the subject.8. The combination of claim 6 , formulated for administration of about 20-350 μg of the Aagonist to an eye of the subject.9. The combination of claim 1 , wherein the Aagonist and the prostaglandin analog are formulated for topical administration to the eye of the subject.11. The kit of claim 10 , wherein the prostaglandin analog is selected from the group consisting of latanoprost claim 10 , travoprost claim 10 , unoprostone and bimatoprost.14. The method of claim 13 , wherein the diseases and conditions caused by elevated IOP in a human are selected from the group consisting of normal-tension glaucoma claim 13 , ocular ...

Synthesis of protected 3'-amino nucleoside monomers

Orthogonally protected 3′-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3′-amino group in the presence of the unprotected nucleoside base.

Novel NNA-DNA Adducts as Biomarkers for Detecting Exposure to Thirdhand Smoke

NNA-derived specific adducts represent an integrated biomarker of exposure to thirdhand smoke (THS) as NNA is unique to THS. The NNA-dG covalent binding adduct could serve as such a biomarker, and play a role in identifying individuals exposed to THS, thus providing critical information for early detection and prevention. 1. A method for detection of prior thirdhand smoke exposure in a sample , comprising the steps ofa. providing a detector which detects the presence or level of a dG adduct and/or NNA in a sample, andb. initiating an notification signal to indicate the presence of a dG adduct and/or NNA, wherein the detection of NNA or any of its dG adducts indicates prior exposure to thirdhand smoke.3. The method of claim 1 , wherein the detection of NNA and/or dG adduct presence or level is detected using mass spectrometry or immunohistochemistry.4. The method of claim 3 , wherein the detection is using immunohistochemistry.5. The method of claim 4 , prior to the providing step (a) claim 4 , the method further comprising the step of contacting the sample with an antibody specific for the NNA and/or dG adduct to be detected.6. The method of claim 1 , wherein the sample is a human tissue or bodily fluid.7. The method of claim 6 , wherein the sample is a bodily fluid selected from the group consisting of blood claim 6 , urine claim 6 , saliva claim 6 , and fecal sample.8. The method of claim 7 , wherein the sample is blood.10. A method for the detection of the presence of DNA damage in a cell as a result of exposure to thirdhand smoke claim 7 , comprising the steps of:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, '(a) providing a cell suspected of exposure to thirdhand smoke; (b) detecting the presence or level of an NNA or dG adduct in said cell of ;'}(b) determining the level of DNA breaks that the cell has encountered due to thirdhand smoke using NNA- or dG adduct—specific probes or compositions to specifically detect NNA or dG adducts as thirdhand smoke ...

ENANTIOMERS OF THE 1',6'-ISOMER OF NEPLANOCIN A

Enantiomers of 1′,6′-isoneplanocin, including derivatives of the enantiomers of 1′,6′-isoneplanocin, are disclosed along with novel synthetic methods. In particular, a substituted cyclopentane epoxide is synthesized into the enantiomers of 1′,6′-isoneplanocin. Enantiomers of carbocyclic nucleoside analogs of 3-deazaneplanocin to provide D- and L-like 1′,6′-iso-3-deazaneplanocin are also disclosed. The small molecule chemotherapeutic compounds beneficially provide DNA and RNA antiviral activity, demonstrating activity towards, for example, human cytomegalovirus, measles, Ebola, norovirus, dengue, vaccinia and HBV. Compounds exhibiting reduced S-adenosylhomocysteine hydrolase inhibitory effects are disclosed and provide improved toxicity profiles in comparison to neplanocin. The invention provides improved prophylactic and/or therapeutic antiviral efficacy. 5. The neplanocin derivative of claim 3 , wherein Z is a halogen.8. The neplanocin derivative of claim 7 , wherein X is CBr.9. A method of therapeutic or prophylactic treatment of a subject against viral infection comprising: administering a therapeutically effective amount of at least one neplanocin derivative of to a subject in need of antiviral therapeutic or prophylactic treatment.10. The method of claim 9 , wherein the administering is by ingestion claim 9 , injection claim 9 , infusion claim 9 , or other bodily administration.11. The method of claim 9 , wherein the virus is a DNA virus.12. The method of claim 9 , wherein the virus is a RNA virus.13. The method of claim 9 , wherein the virus is selected from the group consisting of Arenaviridae claim 9 , Bunyaviridae claim 9 , Coronaviridae claim 9 , Flexiviridae claim 9 , Hepevirus claim 9 , Orthomyxoviridae claim 9 , Paramyxoviridae claim 9 , Picornaviridae claim 9 , Togaviridae claim 9 , Herpesviridae claim 9 , Papovaviridae claim 9 , Poxviridae claim 9 , hepatic viruses claim 9 , and norovirus.14. The method of claim 13 , wherein the virus is human ...

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs. 270.-. (canceled) Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application, are hereby incorporated by reference under 37 CFR 1.57.The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled SEQLISTING067.TXT, created Dec. 19, 2013, which is 728 bytes in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.1. FieldThe present application relates to the fields of chemistry, biochemistry and medicine. More particularly, disclosed herein are nucleotide analogs, pharmaceutical compositions that include one or more nucleotide analogs and methods of synthesizing the same. Also disclosed herein are methods of treating diseases and/or conditions with a nucleotide analog, alone or in combination therapy with one or more other agents.2. DescriptionNucleoside analogs are a class of compounds that have been shown to exert antiviral and anticancer activity both in vitro and in vivo, and thus, have been the subject of widespread research for the treatment of viral infections. Nucleoside analogs are usually therapeutically inactive compounds that are converted by host or viral enzymes to their respective active anti-metabolites, which, in turn, may inhibit polymerases involved in viral or cell proliferation. The activation occurs by a variety of mechanisms, such as the addition of one or more phosphate groups and, or in combination with, other metabolic processes.Some embodiments disclosed herein relate to a compound of Formula (I) or a pharmaceutically acceptable salt thereof.Some embodiments disclosed herein relate to a method of ...