Multicyclic amino acid derivatives and methods of their use

Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders.

Processes for the preparation of isoindole compounds and isotopologues thereof

Processes for the preparation of certain isoindole compounds, and isotopologues thereof, are provided. In some embodiments, the processes comprise catalytic asymmetrical hydrogenation with hydrogen gas or deuterium gas in a solvent containing exchangeable proton or deuterium for proton-deuterium exchange.

Piston type industrial pump parallel using system and method

The invention provides a piston type industrial pump parallel using system and method in a paste filling system, wherein the vacancy rate of equipment can be eliminated, the capability of allocation of system device can be reduced and the operational reliability of the system can be effectively ensured. The piston type industrial pump using system comprises two parallel piston type industrial pumps and a connecting pipeline. The outlet of each piston type industrial pump is sequentially connected with a hose and two hard pipes. The two hard pipes are combined jointly through a converging three-way joint. According to the piston type industrial pump using system provided by the invention, two piston type industrial pumps in small capacity are parallelly used, therefore conventional configuration mode of one pump with a backup is broken. The pumps in small capacity replace pumps in great capacity, and the one-machine capacity of the device is reduced, so that the investment expense of the ...

TRYPTOPHAN HYDROXYLASE INHIBITORS

Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders: 1203-. (canceled)205. The compound of claim 204 , wherein A is optionally substituted aryl.206. The compound of claim 205 , wherein A is optionally substituted phenyl.207. The compound of claim 204 , wherein A is optionally substituted heterocycle.208. The compound of claim 204 , wherein X is —C(R)═ claim 204 , ═C(R)— claim 204 , —C(RR)— claim 204 , —C(R)═C(R)— claim 204 , or —C≡C—.209. The compound of claim 208 , wherein each Ris independently hydrogen or optionally substituted alkyl.210. The compound of claim 204 , wherein X is —O— claim 204 , —C(RR)O— claim 204 , or —OC(RR)—.211. The compound of claim 210 , wherein Ris hydrogen.212. The compound of claim 210 , wherein Ris independently hydrogen or optionally substituted alkyl.213. The compound of claim 204 , wherein E is optionally substituted aryl.214. The compound of claim 213 , wherein E is optionally substituted phenyl.215. The compound of claim 204 , wherein Ris hydrogen or optionally substituted alkyl.216. The compound of claim 204 , wherein Ris hydrogen or optionally substituted alkyl.217. The compound of claim 204 , wherein n is 1.218. A pharmaceutical formulation comprising the compound of and a pharmaceutically acceptable excipient.219. A method of treating irritable bowel syndrome claim 204 , which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of .220. A method of treating carcinoid syndrome claim 204 , which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of .221. A method of treating Crohn's disease claim 204 , which comprises administering to a patient in need thereof a therapeutically effective amount of a compound of . This is a continuation of U.S. application Ser. No. 12/750,278, filed Mar. 30, 2010, which ...

PROCESSES FOR THE PREPARATION OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE FORMS THEREOF

Provided are processes for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable form thereof. 2. The process of claim 1 , wherein step 1.1 and step 1.2 occur in one-pot.3. The process of claim 1 , wherein step 1.1 occurs in the presence of an acid.4. The process of claim 3 , wherein step 1.1 occurs in the presence of RCOOH wherein Ris hydrogen claim 3 , substituted or unsubstituted Calkyl claim 3 , substituted or unsubstituted Chaloalkyl claim 3 , or substituted or unsubstituted Caryl.5. The process of claim 4 , wherein step 1.1 occurs in the presence of formic acid claim 4 , acetic acid claim 4 , trifluoroacetic acid claim 4 , or benzoic acid.6. The process of claim 3 , wherein step 1.1 occurs in the presence of RSOH wherein le is hydrogen claim 3 , substituted or unsubstituted Calkyl claim 3 , substituted or unsubstituted Chaloalkyl claim 3 , or substituted or unsubstituted Caryl.7. The process of claim 6 , wherein step 1.1 occurs in the presence of sulfonic acid claim 6 , benzenesulfonic acid claim 6 , p-toluenesulfonic acid claim 6 , camphorsulfonic acid claim 6 , methanesulfonic acid claim 6 , or trifluoromethanesulfonic acid.8. The process of claim 7 , wherein step 1.1 occurs in the presence of benzenesulfonic acid claim 7 , p-toluenesulfonic acid claim 7 , camphorsulfonic acid claim 7 , or methanesulfonic acid.9. The process of claim 8 , wherein step 1.1 occurs in the presence of benzenesulfonic acid.10. The process of claim 1 , wherein step 1.2 occurs in the presence of a dehydrating agent.11. The process of claim 10 , wherein step 1.2 occurs in the presence of 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide (EDCI) or 2-(1H-benzotriazole-1-yl)-1 claim 10 ,1 claim 10 ,3 claim 10 ,3-tetramethyluronium tetrafluoroborate (TBTU).12. The process of claim 1 , wherein step 1.2 occurs by azeotropic distillation.13. The process of claim 1 ...

PROCESSES FOR THE PREPARATION OF ISOINDOLE COMPOUNDS AND ISOTOPOLOGUES THEREOF

Processes for the preparation of certain isoindole compounds, and isotopologues thereof, are provided. In some embodiments, the processes comprise catalytic assymetrical hydrogenation with hydrogen gas or deuterium gas in a solvent containing exchangeable proton or deuterium for proton-deuterium exchange. 4. The process of claim 1 , wherein Yis hydrogen or deuterium; and Yand Yare both hydrogen or both deuterium.5. The process of claim 4 , wherein Yis hydrogen or deuterium; and Yand Yare both hydrogen or both deuterium claim 4 , wherein not all of Y claim 4 , Y claim 4 , and Yare hydrogen.7. The process of claim 1 , wherein Rand Rare substituted or unsubstituted (C-C)alkoxy claim 1 , or an isotopologue thereof.8. The process of claim 7 , wherein Ris OMe enriched with 0 claim 7 , 1 claim 7 , 2 claim 7 , or 3 deuterium claim 7 , and Ris OEt enriched with 0 claim 7 , 1 claim 7 , 2 claim 7 , 3 claim 7 , 4 claim 7 , or 5 deuterium.9. The process of claim 8 , wherein Ris OCD claim 8 , and Ris OEt.10. The process of claim 8 , wherein Ris OCD claim 8 , and Ris OCDCD.11. The process of claim 1 , wherein Ris Me enriched with 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 deuterium.14. The process of claim 1 , wherein R is methyl enriched with 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 deuterium or cyclopropyl enriched with 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 deuterium.15. The process of claim 1 , wherein the hydrogenation in step (a) occurs with hydrogen gas.16. The process of claim 1 , wherein the hydrogenation in step (a) occurs with deuterium gas.17. The process of claim 1 , wherein the hydrogenation in step (a) occurs in a solvent containing exchangeable proton for proton-deuterium exchange.18. The process of claim 17 , wherein the solvent containing exchangeable proton for proton-deuterium exchange is 2 claim 17 ,2 claim 17 ,2-trifluoroethanol.19. The process of claim 1 , wherein the hydrogenation in step (a) occurs in a solvent containing ...

MK2 INHIBITORS, SYNTHESIS THEREOF, AND INTERMEDIATES THERETO

The present invention provides methods of preparing a MK2 inhibitor, and intermediates related thereto. 4. The method according to claim 11 , wherein the reaction conditions comprise an acid.5. The method according to claim 16 , wherein the acid is HCl or BSA.6. The method according to any one of - claim 16 , wherein a compound of formula 1-10 is provided as an HCl salt.7. The method according to claim any one of - claim 16 , wherein a compound of formula 1-10 is provided as a BSA salt12. The method according to any one of claim 11 , wherein the reaction conditions comprise an activating compound.14. The method according to claim 13 , wherein the reaction conditions comprise a peroxide reagent.16. The method according to claim 15 , wherein the reaction conditions comprise a nitrite compound.17. The method according to or claim 15 , wherein the reaction conditions further comprise a bromide source.20. The method according to claim 19 , wherein the reaction conditions comprise a cyanating agent. The present application claims priority to U.S. Provisional Patent Application No. 62/472,024, filed on Mar. 16, 2017, the entirety of which is hereby incorporated by reference.The present invention relates to compounds useful as inhibitors of MK2 kinases. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The search for new therapeutic agents has been greatly aided in recent years by a better understanding of the structure of enzymes and other biomolecules associated with diseases. One important class of enzymes that has been the subject of extensive study is protein kinases.Protein kinases constitute a large family of structurally related enzymes that are responsible for the control of a variety of signal transduction processes within the cell. Protein kinases are thought to have evolved from a common ancestral gene due to the ...

MK2 INHIBITORS, SYNTHESIS THEREOF, AND INTERMEDIATES THERETO

The present invention provides methods of preparing a MK2 inhibitor, and intermediates related thereto. 4. The method according to claim 11 , wherein the reaction conditions comprise an acid.5. The method according to claim 16 , wherein the acid is HCl or BSA.6. The method according to any one of - claim 16 , wherein a compound of formula 1-10 is provided as an HCl salt.7. The method according to claim any one of - claim 16 , wherein a compound of formula 1-10 is provided as a BSA salt12. The method according to any one of claim 11 , wherein the reaction conditions comprise an activating compound.14. The method according to claim 13 , wherein the reaction conditions comprise a peroxide reagent.16. The method according to claim 15 , wherein the reaction conditions comprise a nitrite compound.17. The method according to or claim 15 , wherein the reaction conditions further comprise a bromide source.20. The method according to claim 19 , wherein the reaction conditions comprise a cyanating agent. The present application claims priority to U.S. Provisional Patent Application No. 62/472,024, filed on Mar. 16, 2017, the entirety of which is hereby incorporated by reference.The present invention relates to compounds useful as inhibitors of MK2 kinases. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.The search for new therapeutic agents has been greatly aided in recent years by a better understanding of the structure of enzymes and other biomolecules associated with diseases. One important class of enzymes that has been the subject of extensive study is protein kinases.Protein kinases constitute a large family of structurally related enzymes that are responsible for the control of a variety of signal transduction processes within the cell. Protein kinases are thought to have evolved from a common ancestral gene due to the ...

PROCESSES FOR THE PREPARATION OF ISOINDOLE COMPOUNDS AND ISOTOPOLOGUES THEREOF

Processes for the preparation of certain isoindole compounds, and isotopologues thereof, are provided. In some embodiments, the processes comprise catalytic assymetrical hydrogenation with hydrogen gas or deuterium gas in a solvent containing exchangeable proton or deuterium for proton-deuterium exchange. 125-. (canceled)27. The process of claim 26 , wherein Yis hydrogen or deuterium; and Yand Yare both hydrogen or both deuterium.28. The process of claim 27 , wherein Yis hydrogen or deuterium; and Yand Yare both hydrogen or both deuterium claim 27 , wherein not all of Y claim 27 , Y claim 27 , and Yare hydrogen.30. The process of claim 26 , wherein Rand Rare substituted or unsubstituted (C-C)alkoxy claim 26 , or an isotopologue thereof.31. The process of claim 30 , wherein Ris OMe enriched with 0 claim 30 , 1 claim 30 , 2 claim 30 , or 3 deuterium claim 30 , and Ris OEt enriched with 0 claim 30 , 1 claim 30 , 2 claim 30 , 3 claim 30 , 4 claim 30 , or 5 deuterium.32. The process of claim 31 , wherein Ris OCD claim 31 , and Ris OEt.33. The process of claim 31 , wherein Ris OCD claim 31 , and Ris OCDCD.34. The process of claim 26 , wherein Ris Me enriched with 0 claim 26 , 1 claim 26 , 2 claim 26 , or 3 deuterium.37. The process of claim 26 , wherein the hydrogenation in step (a) occurs with hydrogen gas.38. The process of claim 26 , wherein the hydrogenation in step (a) occurs with deuterium gas.39. The process of claim 26 , wherein the hydrogenation in step (a) occurs in a solvent containing exchangeable proton for proton-deuterium exchange.40. The process of claim 39 , wherein the solvent containing exchangeable proton for proton-deuterium exchange is 2 claim 39 ,2 claim 39 ,2-trifluoroethanol.41. The process of claim 26 , wherein the hydrogenation in step (a) occurs in a solvent containing exchangeable deuterium for proton-deuterium exchange.42. The process of claim 41 , wherein the solvent containing exchangeable deuterium for proton-deuterium exchange is 2 claim ...

PROCESSES FOR THE PREPARATION OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE FORMS THEREOF

Provided are processes for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable form thereof. 167-. (canceled)68. A process to increase the enantiopurity of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2 ,6-dione , or a salt , solvate , or solvate of salt thereof , comprising recrystallization or trituration of a first sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2 ,6-dione , or a salt , solvate , or solvate of salt thereof , in a solvent or a mixture of solvents , resulting in a second sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2 ,6-dione , or a salt , solvate , or solvate of salt thereof , wherein the second sample has a higher ee than the first sample.6970-. (canceled)71. The process of claim 68 , wherein the enantiopurity is increased by recrystallization.72. The process of claim 68 , wherein the enantiopurity is increased by trituration.73. The process of claim 68 , wherein the enantiopurity is increase by 10% or more.74. The process of claim 73 , wherein the enantiopurity is increase by 20% or more.75. The process of claim 68 , wherein the first sample is in the anhydrous freebase form.76. The process of claim 68 , wherein the first sample is in the freebase hydrate form.77. The process of claim 68 , wherein the first sample is in the freebase THF solvate form.78. The process of claim 68 , wherein the first sample is in the HCl salt form.79. The process of claim 68 , wherein the first sample is in the anhydrous HCl salt form.80. The process of claim 68 , wherein the ee of the first sample is from 25% to about 90%.81. The process of claim 80 , wherein the ee of the first sample is from 50% to about 80%.82. The process of claim 68 , wherein the solvent is water claim 68 , diethyl ether claim 68 , 1 claim 68 ,4-dioxane ...

4-phenyl-6-(2,2,2-trifluoro-1-phenyl ethoxy) pyrimidine compounds, solid dosage form and composition

compostos baseados em 4-fenil-6-(2,2,2-triflúor-1-fenil etoxi) pirimidina e processos de usos dos mesmos. a presente invenção refere-se a compostos de fórmula i, que são mostrados, assim como composições compreendendo os mesmos e processos de seu uso dos mesmos para tratar, prevenir e/ou gerenciar doenças e distúrbios. compounds based on 4-phenyl-6-(2,2,2-trifluoro-1-phenyl ethoxy) pyrimidine and processes for using them. the present invention relates to compounds of formula I, which are shown, as well as compositions comprising the same and processes of their use thereof to treat, prevent and/or manage diseases and disorders.

Multicyclic amino acid derivatives and methods of their use

Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders.

Methods of using 4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds

Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and/or manage diseases and disorders:

4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

Methods of using 4-Phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-Based Compounds

Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and/or manage diseases and disorders:

Multicyclic amino acid derivatives and methods of their use

Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders:

MK2 inhibitors, synthesis thereof, and intermediates thereto

The present invention provides methods of preparing a MK2 inhibitor, and intermediates related thereto.

COMPOUNDS BASED ON 4-PHENYL-6- (2,2,2-TRIFLUOR-1-PHENYL ETOXY) PYRIMIDINE AND USES PROCESSES

Compounds based on 4-phenyl-6- (2,2,2-trifluoro-1-phenylethoxy) -pyrimidine and methods for their use

Un compuesto de la fórmula: o una sal o solvato farmacéuticamente aceptable de las mismas, en la que: cada R1 es independientemente halógeno, hidrógeno, C(O)RA, ORA, NRBRC, S(O2)RA o alquilo, alquil-arilo o alquil- heterociclo; R2 es independientemente halógeno, hidrógeno, C(O)RA, ORA, NRBRC, S(O2)RA o alquilo, alquil-arilo o alquil- heterociclo; R3 es hidrógeno, C(O)RA, C(O)ORA o alquilo, alquil-arilo, alquil-heterociclo, arilo o heterociclo; R4 es hidrógeno o alquilo, alquil-arilo, alquil-heterociclo, arilo o heterociclo; cada RA es independientemente hidrógeno o alquilo, alquil-arilo o alquil-heterociclo; cada RB es independientemente hidrógeno o alquilo, alquil-arilo o alquil-heterociclo; cada RC es independientemente hidrógeno o alquilo, alquil-arilo o alquil-heterociclo; m es 1-4, cada R5 es independientemente halógeno, hidrógeno, C(O)RA, ORA, NRBRC, S(O2)RA o alquilo, alquil-arilo o alquil- heterociclo; y n es 1-3. A compound of the formula: or a pharmaceutically acceptable salt or solvate thereof, wherein: each R1 is independently halogen, hydrogen, C (O) RA, ORA, NRBRC, S (O2) RA, or alkyl, alkyl-aryl or alkyl heterocycle; R2 is independently halogen, hydrogen, C (O) RA, ORA, NRBRC, S (O2) RA or alkyl, alkyl aryl or alkyl heterocycle; R3 is hydrogen, C (O) RA, C (O) ORA, or alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle; R4 is hydrogen or alkyl, alkyl aryl, alkyl heterocycle, aryl, or heterocycle; each RA is independently hydrogen or alkyl, alkyl aryl or alkyl heterocycle; each RB is independently hydrogen or alkyl, alkyl aryl or alkyl heterocycle; each RC is independently hydrogen or alkyl, alkyl aryl or alkyl heterocycle; m is 1-4, each R5 is independently halogen, hydrogen, C (O) RA, ORA, NRBRC, S (O2) RA or alkyl, alkyl aryl or alkyl heterocycle; and n is 1-3.

processes for the preparation of (s) -3- (4 - ((4- (morpholinomethyl) benzyl) oxy) -1-oxoisoindolin-2-yl) piperidine-2,6-dione and pharmaceutically acceptable forms thereof

resumo “processos para a preparação de (s) -3- (4 - ((4- (morfolinometil) benzil) oxi) -1-oxoisoindolin-2-il) -piperidina-2,6-diona e formas farmaceuticamente aceitáveis da mesma.” são fornecidos processos para a preparação de 3-(4 -((4-(morfolinometil)benzil)oxi) -1-oxoisoindolino-2-il)piperidina-2,6-diona enantiomericamente enriquecida ou enantiomericamente pura, ou uma forma farmaceuticamente aceitável da mesma. 1 1 / 1 abstract “processes for the preparation of (s)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)-piperidine-2,6-dione and pharmaceutically acceptable forms thereof .” Processes are provided for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolino-2-yl)piperidine-2,6-dione, or an pharmaceutically acceptable thereof. 1 1 / 1

4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use.

Se describen compuestos de la fórmula 1, así como composiciones que los comprenden y métodos de su uso para tratar, evitar y/o administrar enfermedades y desordenes: (ver fórmula).

Tryptophan hydroxylase inhibitors

Compounds of formulae I and II are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and manage serotonin-mediated diseases and disorders:

multicyclic amino acid derivatives, pharmaceutical formulations comprising them, as well as their preparation methods and their uses

DERIVADOS DE AMINOáCIDO MULTICìCLICOS,FORMULAçãO FARMACêUTICA COMPREENDENDO OS MESMOS, BEM COMO SEUS MéTODOS DE PREPARAçãO E SEUS USOS. Compostos de fórmulas I e II são descritas, bem como composições compreendendo-os e métodos de seu uso para tratar, prevenir e controlar doenças e distúrbios mediados por serotonina: MULTICYCLIC AMINO ACID DERIVATIVES, PHARMACEUTICAL FORMULATION UNDERSTANDING THE SAME AS WELL AS THEIR PREPARATION METHODS AND THEIR USES. Compounds of formulas I and II are described, as well as compositions comprising them and methods of their use to treat, prevent and control serotonin-mediated diseases and disorders:

4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

Processes for the preparation of (s)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable forms thereof

Provided are processes for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable form thereof.

Processes for the preparation of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidin-2,6-dione and acceptable dosage forms thereof

Un procedimiento para aumentar la enantiopureza de clorhidrato de (S)-3-(4-((4-(morfolinometil)bencil)oxi)-1- oxoisoindolin-2-il)piperidin-2,6-diona o un solvato del mismo, que comprende la recristalización o la trituración de una muestra de clorhidrato de (S)-3-(4-((4-(morfolinometil)bencil)oxi)-1-oxoisoindolin-2-il)piperidin-2,6-diona o un solvato del mismo, en metanol, en donde el exceso enantiomérico (ee) de la muestra es del 0% al 95%, y la enantiopureza se incrementa en un 1%, 5%, 10%, 15%, 20%, 25%, 30% o más. A process for increasing the enantiopurity of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof , comprising recrystallization or trituration of a sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidin-2,6-dione hydrochloride or a solvate thereof, in methanol, where the enantiomeric excess (ee) of the sample is from 0% to 95%, and the enantiopurity is increased by 1%, 5%, 10%, 15%, 20%, 25%, 30% or more.

Multicyclic amino acid derivatives and methods of their use

Disclosed are compounds of formulae I and II, wherein the substituents are as defined in the specification, as well as compositions comprising them. The compounds inhibit TPH1, the isoform of tryptophan hydroxylase which is expressed in the periphery, primarily in the gastrointestinal (GI) tract, and are therefore useful to treat, prevent and manage serotonin-mediated diseases and disorders.

4-phenyl-6-(2,2,2-trifluoro-1-phenylethoxy)pyrimidine-based compounds and methods of their use

Compounds of formula I are disclosed, as well as compositions comprising them and methods of their use to treat, prevent and/or manage diseases and disorders.

Multicyclic amino acid derivatives and methods of their use

Data transmission method, apparatus, and system, and computer-readable storage medium

This application discloses a data transmission method. The method includes: performs bit multiplexing to obtain a plurality of third data streams based on a plurality of first data streams and a plurality of second data streams, where the first data stream and the second data stream belong to different virtual lane groups; and transmits the plurality of third data streams to a second module, to enable the second module to obtain a plurality of fourth data streams based on the plurality of third data streams, where any fourth data stream is obtained by performing bit multiplexing on any second quantity of third data streams in the plurality of third data streams. Bit multiplexing is performed on the obtained data streams, so that the method can improve a transmission rate of the data stream and reduce a frame loss ratio of a system.

Processes for the preparation of (s)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl) methyl)benzyl) amino)isoindoline-1,3-dione

Processes for the preparation of (s)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl) methyl)benzyl) amino)isoindoline-1,3-dione

Provided herein are processes for the preparation of (S)-2-(2,6- dioxopipelidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-l-yl) methyl) benzyl)amino)isoindoline-l, 3-dione, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, which is useful for treating, preventing, and managing various disorders. Also provided are solid forms of various intermediates and products obtained from the processes.

Processos para a preparação de (s)-2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3-morfolinoazetidin-1-il)metil)benzil)amino)isoindolina-1,3-diona

processos para a preparação de (s)- 2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3 morfolinoazetidin-1-il)metil)benzil)amino)isoindolina-1,3-diona. a presente invenção refere-se a processos para a preparação de (s)-2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3-morfolinoazetidin-1-il)metil)benzil)amino)isoindolina-1,3-diona, ou um sal, solvato, hidrato, enantiômero, mistura de enantiômeros ou isotopólogo da mesma, que é útil para o tratamento, a prevenção e o controle de vários distúrbios. também são fornecidas formas sólidas de vários intermediários e produtos obtidos a partir dos processos.

Data transmission method, apparatus, and system, and computer-readable storage medium

This application discloses a data transmission method. The method includes: performs bit multiplexing to obtain a plurality of third data streams based on a plurality of first data streams and a plurality of second data streams, where the first data stream and the second data stream belong to different virtual lane groups; and transmits the plurality of third data streams to a second module, to enable the second module to obtain a plurality of fourth data streams based on the plurality of third data streams, where any fourth data stream is obtained by performing bit multiplexing on any second quantity of third data streams in the plurality of third data streams. Bit multiplexing is performed on the obtained data streams, so that the method can improve a transmission rate of the data stream and reduce a frame loss ratio of a system.

Decoding method and apparatus

A decoding method and an apparatus are provided. A decoder includes a type detection module, a decoding and prediction module, a state determining module, and an output processing module. The type detection module is configured to detect a type of a to-be-decoded code block. The decoding and prediction module is configured to: decode the to-be-decoded code block, and obtain a predicted decoding mode of the to-be-decoded code block. The state determining module is configured to select a decoding mode from the predicted decoding mode of the to-be-decoded code block. The output processing module is configured to update a decoding result based on the decoding mode selected by the state determining module. The decoder further includes a delay device, configured to delay outputting received data by at least one clock cycle. This application can enable different bus bit widths or different processes to have compatible requirements on a time sequence of implementing decoding at a physical coding sublayer, and improve system flexibility.

Processes for the preparation of (s)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl) methyl)benzyl) amino)isoindoline-1,3-dione

Decoding method and apparatus

A decoding method and an apparatus are provided. A decoder includes a type detection module, a decoding and prediction module, a state determining module, and an output processing module. The type detection module is configured to detect a type of a to-be-decoded code block. The decoding and prediction module is configured to: decode the to-be-decoded code block, and obtain a predicted decoding mode of the to-be-decoded code block. The state determining module is configured to select a decoding mode from the predicted decoding mode of the to-be-decoded code block. The output processing module is configured to update a decoding result based on the decoding mode selected by the state determining module. The decoder further includes a delay device, configured to delay outputting received data by at least one clock cycle. This application can enable different bus bit widths or different processes to have compatible requirements on a time sequence of implementing decoding at a physical coding sublayer, and improve system flexibility.

Processes for the preparation of (s)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione

Provided herein are processes for the preparation of (S)-2-(2,6-dioxopipelidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl) methyl) benzyl)amino)isoindoline-1, 3-dione, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, which is useful for treating, preventing, and managing various disorders. Also provided are solid forms of various intermediates and products obtained from the processes.

Processes for the preparation of (s)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl) methyl)benzyl) amino)isoindoline-1,3-dione

Provided herein are processes for the preparation of (S)-2-(2,6- dioxopipelidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-l-yl) methyl) benzyl)amino)isoindoline-l, 3-dione, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, which is useful for treating, preventing, and managing various disorders. Also provided are solid forms of various intermediates and products obtained from the processes.

Procesos para la preparacion de (s)-2-(2,6-dioxopiperidin-3-il)-4- ((2-fluoro-4-((3-morfolinoazetidin-1-il)metil)bencil)amino)isoind olin-1,3-diona.

En el presente documento se proporcionan procesos para la preparación de (S)-2-(2,6-dioxopiperidin-3-il)-4-((2-fluoro-4-((3- morfolinoazetidin-1-il)metil)bencil)amino)isoindolin-1,3-diona, o una sal, solvato, hidrato, enantiómero, mezcla de enantiómeros o isotopólogo de la misma, que es útil para tratar, prevenir y gestionar diversos trastornos. También se proporcionan formas sólidas de diversos intermediarios y productos que se obtienen a partir de los procesos.

Decoding method and apparatus

Sending method and apparatus, receiving method and apparatus, system, device, and storage medium

This application discloses a sending method, a receiving method, an apparatus, a system, a device, and a storage medium. The receiving method includes: obtaining an encoded data block, where the encoded data block includes a plurality of data blocks, a plurality of first parity bits, and an FEC parity bit, the plurality of first parity bits are in one-to-one correspondence with the plurality of data blocks, and the FEC parity bit corresponds to the plurality of data blocks; and then checking the corresponding data blocks based on the plurality of first parity bits and/or the FEC parity bit, to obtain a decoding result of the encoded data block. The method can not only retain an error correction capability of a high-gain FEC code, but also reduce impact of high-gain FEC on a latency, so that requirements for a low latency and an FEC high gain can be met at the same time.

Sending method, receiving method, apparatus, system, device, and storage medium

A sending method, a receiving method, an apparatus, a system, a device, and a storage medium. The receiving method includes: obtaining an encoded data block, where the encoded data block includes a plurality of data blocks, a plurality of first parity bits, and an FEC parity bit, the plurality of first parity bits are in one-to-one correspondence with the plurality of data blocks, and the FEC parity bit corresponds to the plurality of data blocks; and then checking the corresponding data blocks based on the plurality of first parity bits and/or the FEC parity bit, to obtain a decoding result of the encoded data block.