STIGMASTEROL-RICH PHYTOSTEROL COMPOSITION AND USE

A stigmasterol-rich phytosterol composition is prepared wherein the composition comprises at least 50% stigmasterol, based on the total weight of phytosterols, no more than 1000 ppm water, no more than 50 ppm ethanol, and wherein stigmasterol is at least 98% in the anhydrous form. A ready-to-freeze beverage is provided comprising the stigmasterol-rich composition and water, with optional additives. A frozen beverage is prepared from the ready-to-freeze beverage as a pourable slush. There are further provided processes to prepare the ready-to-freeze beverage and the frozen slush beverage. 1. A process to prepare a stigmasterol-rich composition which comprises heating a crude stigmasterol phytosterol blend under conditions of time and temperature , to reduce the amount of water and ethanol or to convert stigmasterol in amorphous or hydrated crystal form , to provide a stigmasterol-rich phytosterol composition comprising at least 50% stigmasterol , based on total weight of phytosterols , wherein stigmasterol is at least 98% in the anhydrous form , and the composition comprises no more than 1000 ppm water and no more than 50 ppm ethanol.2. The process of wherein the stigmasterol-rich composition comprises at least 85% stigmasterol claim 1 , based on total weight of phytosterols claim 1 , and no more than 30 ppm ethanol.3. The process of wherein the heating is performed in an oven.4. The process of wherein the conditions of time and temperature are 90 minutes and 135° C.5. The process of wherein the heating is performed in a fluidized bed or a tumble dryer.6. A process to prepare an improved stigmasterol ice nucleating agent claim 1 , said process comprising: providing a sample of crude stigmasterol having more than 1000 ppm water; heating said crude stigmasterol under conditions of time and temperature to convert substantially all of the crude stigmasterol to anhydrous stigmasterol having less than 1000 ppm water.7. The process of wherein the heating is performed in an ...

Derivatives of allopregnanolone and of epiallopregnanolone and uses thereof for treating a neuropathological condition

The présent invention relates to novel neurosteroids, especially derivatives of allopregnanolone and of epiallopregnanolone of formula (I) and the uses thereof as médicament for the treatment of neuropathologies, in particular neuropathies induced by the chemotherapy of a cancer. Thèse molécules according to the invention have both preventative and curative effects. The neurosteroids according to the invention may also be of use in the treatment of neurodegenerative disorders, in particular for preventing neuronal cell death. They may thus be used as neuroprotectants and/or as an agent that stimulâtes neuronal prolifération.

DERIVATIVES OF ALLOPREGNANOLONE AND OF EPIALLOPREGNANOLONE AND USES THEREOF FOR TREATING A NEUROPATHOLOGICAL CONDITION

The present invention relates to novel neurosteroids, especially derivatives of allopregnanolone and of epiallopregnanolone of formula (I) and the uses thereof as medicament for the treatment of neuropathologies, in particular neuropathies induced by the chemotherapy of a cancer. These molecules according to the invention have both preventative and curative effects. The neurosteroids according to the invention may also be of use in the treatment of neurodegenerative disorders, in particular for preventing neuronal cell death. They may thus be used as neuroprotectants and/or as an agent that stimulates neuronal proliferation. 2. The derivative according to claim 1 , wherein{'sup': '1', 'Ris a group chosen among the 3-alpha or 3-beta O-allyl groups, the 3-alpha or 3-beta O-propargyl groups, the 3-alpha or 3-beta O-glycol groups, the 3-alpha or 3-beta O-PEG groups, the 3-alpha or 3-beta O-glycol-allyl groups and 3-alpha or 3-beta O-PEG-allyl groups,'}A is a carbon atom substituted by an atom chosen among 5-H alpha and 5-H beta and B is a methylene group; orA and B are carbon atoms forming a 5,6-double bond;C is a carbon atom substituted by an atom chosen among 14-H alpha, 14-H beta, 14-alpha OH and 14-beta OH and D is a methylene group; orC and D are carbon atoms forming a 14,15-double bond;{'sup': 2', '2', '2, 'F is a carbon atom substituted by an atom chosen among 17-H alpha and 17-H beta, and E is a methylene group or a carbon atom substituted by a group chosen among 16-alkyl-alpha, 16-alkyl-beta, 16-OR-alpha and 16-OR-beta, with Ra group chosen among allyl, propargyl, glycol, PEG, glycol-allyl, PEG-allyl, or'}{'sup': 2', '2', '2', '2', '2', '2, 'F is a carbon atom substituted by a group chosen among 17-alkyl-alpha, 17-alkyl-beta, 17-OR-alpha and 17-OR-beta, with Ra group chosen among allyl, propargyl, glycol, PEG, glycol-allyl, PEG-allyl, and E is a methylene group or a carbon atom substituted by a group chosen among 16-alkyl-alpha, 16-alkyl-beta, 16-OR-alpha and ...

METHODS FOR PREPARATION OF BILE ACIDS AND DERIVATIVES THEREOF

The present application relates to a method of preparing compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, Ris H, α-OH, β-OH, or an oxo group. 3. The method of claim 2 , wherein the deprotecting in step 2 and the hydrolyzing in step 3 occur in a single step.6. The method of or claim 2 , wherein the deprotecting in step 4 and the hydrolyzing in step 5 occur in a single step.8. The method of claim 7 , wherein the stereoselective reduction comprises hydrogenation.9. The method of claim 8 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.11. The method of claim 10 , wherein the stereoselective reduction comprises hydrogenation.12. The method of claim 11 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.14. The method of claim 13 , wherein the stereoselective reduction comprises hydrogenation.15. The method of claim 14 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.19. The method of claim 18 , wherein the stereoselective reduction of 15 to 16A comprises reacting 15 with K-Selectride.20. The method of claim 18 , wherein the stereoselective reduction of 16A to 17 comprises hydrogenation.21. The method of claim 20 , wherein the hydrogenation comprises reacting 16A with a catalyst and hydrogen gas.23. The method of claim 22 , wherein stereoselective reduction of 15 to 16B comprises reacting 15 with NaBHand CeCl.7HO.24. The method of claim 22 , wherein the stereoselective reduction of 16B to 18 comprises hydrogenation.25. The method of claim 24 , wherein the hydrogenation comprises reacting 16B with a catalyst and hydrogen gas. Bile acids and bile acid derivatives are useful in the treatment and prevention of diseases. Bile acids have been shown to induce internalization of the TGR5 fusion protein from the cell membrane to the cytoplasm (Kawamata et al., 2003, J. Biol. Chem. 278, 9435). TGR5 is associated with the intracellular accumulation of ...

Neuroactive steroids, compositions, and uses thereof

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R a , G, X, Y, Z, and n are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

OXYSTEROLS AND METHODS OF USE THEREOF

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions. 2. (canceled)3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted Calkyl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH claim 1 , —CF claim 1 , —CHOCH claim 1 , —CH(CH)(CF) claim 1 , —CHCH claim 1 , or —CH(CH).6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHor —CHCH.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted or unsubstituted ethyl claim 1 , substituted or unsubstituted isopropyl claim 1 , or substituted or unsubstituted tert-butyl.911-. (canceled)12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein represents a single bond.1617-. (canceled)2021-. (canceled)23. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.24. A method of inducing sedation or anesthesia comprising administering to a subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition thereof.25. A method for treating a disorder claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition thereof; wherein the disorder is a gastrointestinal (GI) disorder ...

NEUROACTIVE 13, 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS

The present disclosure is generally directed to neuroactive 13, 17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein the C—H is in the alpha configuration.4. The compound of claim 1 , wherein Ris H or —OCH.5. The compound of claim 1 , wherein Ris H or —OCH.6. The compound of claim 1 , wherein Ris methyl or —CHOCH.7. The compound of claim 1 , wherein Ris H or —OCH.8. The compound of claim 1 , wherein Ris —CH═CHor —C(O)CH.9. The compound of claim 1 , wherein Ris selected from the group consisting of —CH═CH claim 1 , ethyl claim 1 , —C(O)CH claim 1 , hydroxy alkyl claim 1 , and haloalkyl.10. The compound of claim 9 , wherein Ris hydroxyl alkyl claim 9 , and further is selected from the group consisting of —C(OH)CHand —CH(OH).11. The compound of claim 9 , wherein Ris —CHCl.12. The compound of claim 1 , wherein Ris H.15. A pharmaceutically acceptable salt of a compound of .16. A pharmaceutical composition comprising a compound of claim 1 , a pharmaceutically acceptable salt thereof claim 1 , or a combination of two or more thereof claim 1 , and a pharmaceutically acceptable carrier. This application is a continuation application and claims priority benefit of U.S. patent application Ser. No. 14/191,740, filed on Feb. 27, 2014 and which claims priority benefit of U.S. Provisional Patent Application Ser. No. 61/771,350, filed on Mar. 1, 2013, the entire contents of which are incorporated herein by reference.This invention was made with government support under NIH Grant #GM47969, awarded by the National Institute of Health. The Government has certain rights in the invention.The present disclosure is generally directed to novel compounds ...

Neuroactive steroids, compositions, and uses thereof

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R a , G, X, Y, Z, and n are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

PREPARATION OF BILE ACIDS AND INTERMEDIATES THEREOF

Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided. 2. The composition of claim 1 , further comprising a solvent.3. The composition of claim 1 , wherein the hydrogenation catalyst comprises Pd/C.4. The composition of claim 2 , wherein the solvent is DMF.7. The composition of claim 6 , further comprising a solvent.8. The composition of claim 6 , wherein the olefination reagent is PhPCHCHBr.11. The composition of claim 10 , wherein the composition further comprises a solvent.12. The composition of claim 10 , wherein —OP is —OAc and —COR is —COMe.1316.-. (canceled)18. The composition of claim 17 , wherein the composition further comprises a solvent.19. The composition of claim 17 , wherein the reducing agent is lithium tri-tert-butoxyaluminum hydride.20. The composition of claim 17 , wherein —OP is —OAc and —COR is —COMe. This application is a divisional of U.S. patent application Ser. No. 14/696,204, filed Apr. 24, 2015, which is a divisional of U.S. patent application Ser. No. 13/752,175, filed Jan. 28, 2013; which is a continuation of U.S. patent application Ser. No. 13/010,727, filed Jan. 20, 2011, issued as U.S. Pat. No. 8,362,285; which is a divisional of U.S. patent application Ser. No. 12/613,969, filed Nov. 6, 2009, issued as U.S. Pat. No. 7,994,351 on Aug. 9, 2011; which is a continuation of U.S. patent application Ser. No. 12/153,446, filed May 16, 2008, issued as U.S. Pat. No. 7,902,387 on Feb. 16, 2011; which claims the benefit under 35 U.S.C. 119(a) of United Kingdom Application Serial No. 0807615.0, filed Apr. 25, 2008; each of which are hereby incorporated by reference into this application in their entirety.The present invention relates to the synthesis of deoxycholoic acid and pharmaceutically acceptable salts and intermediates thereof.Rapid removal of body fat is an age-old ideal, and many substances have been claimed to accomplish such results, although few have shown results. “Mesotherapy”, or the use of ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain,traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 141-. (canceled)60. The method of claim 42 , wherein the method is a method of treating a sleep disorder.61. The method of claim 60 , wherein the sleep disorder is insomnia.62. The method of claim 42 , wherein the method is a method of treating a mood disorder.63. The method of claim 42 , wherein the mood disorder is depression.64. The method of claim 63 , wherein the depression is postnatal depression.65. The method of claim 64 , wherein the compound or pharmaceutical composition is administered orally. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from −70 mV to −50 mV). This effect is mediated by postsynaptic ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 237-. (canceled)39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.40. The method of or wherein the compound is administered orally claim 38 , subcutaneously claim 38 , intravenously claim 38 , or intramuscularly.41. The method of or wherein the compound is administered chronically. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane.Neurotransmitters are stored in presynaptic vesicles and are released under the ...

ANTAGONISTS OF CB1 RECEPTOR

The invention relates to an antagonist of CB1 receptor for use in the treatment of a pathologic condition or disorder selected from the group consisting of bladder and gastrointestinal disorders; inflammatory diseases; cardiovascular diseases; nephropathies; glaucoma; spasticity; cancer; osteoporosis; metabolic disorders; obesity; addiction, dependence, abuse and relapse related disorders; psychiatric and neurological disorders; neurodegenerative disorders; autoimmune hepatitis and encephalitis; pain; reproductive disorders and skin inflammatory and fibrotic diseases. 130-. (canceled)32. The method according to claim 31 , wherein said compound is not substantially converted into active pregnenolone down stream derivatives after administration to a subject.34. The pregnenolone derivative compound according to claim 33 , wherein said compound is 17α-Methylprogesterone or 17α-Benzylprogesterone.36. The method according to claim 35 , wherein said compound is 5-pregnen-3β-O-benzyl-20-one claim 35 , 3β-Aminopregnenolone or 5-pregnen-3β-azido-20-one.38. The method according to claim 37 , wherein said compound is 17α-Allyl-3β-methoxypregnenolone claim 37 , 17α-Benzyl-3β-fluoropregnenolone claim 37 , 3β-Fluoro-17α-methylpregnenolone claim 37 , 3β-Methoxy-17α-methylpregnenolone claim 37 , 17α-Benzyl-3β-methoxypregnenolone claim 37 , 3β-Benzyloxy-17α-methylpregnenolone or 17α-Benzyl-3β-benzyloxypregnenolone.40. The method according to claim 39 , wherein said compound is 17α-Benzylpregnenolone claim 39 , 17α-Ethylpregnenolone claim 39 , 17α-Methylpregnenolone or 17-Methoxypregnenolone.42. The method according to claim 41 , wherein said compound is 20-Deoxypregnenolone or 20-Methylamino-5-pregnen-3β-ol.44. The method according to wherein said compound is 5 claim 43 ,16-Pregnadien-20-one.45. The method according to wherein the bladder and gastrointestinal disorder is selected from the group consisting of liver fibrosis; liver steatosis; non-alcoholic steatohepatitis (NASH); liver ...

Methods for preparing deoxycholic acid

The present invention discloses method for preparing deoxycholic acid (DCA) or an ester thereof or a pharmaceutically acceptable salt thereof. Said compounds may be applied to remove a fat deposition.

19-nor c3, 3-disubstituted c21-c-bound heteroaryl steroids and methods of use thereof

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein, , R 1 , R 2 , R 3a , R 3b , R 4a , and R 4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Described herein are neuroactive steroids of the Formula (I): 2. The compound of claim 1 , wherein Ris substituted or unsubstituted Calkyl (e.g. claim 1 , haloalkyl).3. The compound of any one of the preceding claims claim 1 , wherein Ris methyl or CF.4. The compound of any one of the preceding claims claim 1 , wherein Ris methyl.5. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.6. The compound of any one of the preceding claims claim 1 , wherein Ris methyl and Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein represents a single bond.11. The compound of any one of the preceding claims claim 1 , wherein A is heterocyclyl or heteroaryl (e.g. claim 1 , nitrogen-containing heterocyclyl or a nitrogen-containing heteroaryl).12. The compound of any one of the preceding claims claim 1 , wherein A is monocyclic or bicyclic.13. The compound of any one of the preceding claims claim 1 , wherein A is substituted with at least one R claim 1 , wherein Ris Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocyclyl claim 1 , Chaloalkyl claim 1 , halogen claim 1 , cyano claim 1 , —OR claim 1 , —C(═O)OR claim 1 , —SR claim 1 , —S(═O)R claim 1 , or S(═O)R claim 1 , wherein Ris hydrogen or Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocyclyl claim 1 , or Chaloalkyl claim 1 , and Ris Calkyl or Ccarbocyclyl.14. The compound of claim 13 , wherein Ris Calkyl claim 13 , halogen claim 13 , or cyano.15. The compound of any one of - claim 13 , wherein A is substituted with 1-3 instances of R.17. The compound of claim 16 , wherein Ris substituted or unsubstituted Calkyl (e.g. claim 16 , haloalkyl).18. The compound of any one of - claim 16 , wherein Ris methyl or CF.19. The compound of any one of - claim 16 , wherein Ris methyl.20. The compound of any one of - claim 16 , wherein Ris hydrogen.21. The compound of any one of - claim 16 , wherein Ris methyl and Ris hydrogen.22. The compound of any one of - claim ...

Synthesis of a substituted indene derivative

This invention is directed to methods of preparing AQX-1125 having the formula: This invention is also directed to intermediates utilized in the methods of preparing AQX-1125.

Compounds for targeted therapies of castration resistant prostate cancer

The present invention generally relates to new compounds for therapeutic uses. In particular, this disclosure relates to novel tetracyclic compounds useful for treatment of cancer, especially castration resistant prostate cancer. Pharmaceutical composition matters and methods for treating a cancer patient by administering therapeutically effective amounts of such compound alone or together with other therapeutics are within the scope of this disclosure.

METHODS FOR PREPARING DEOXYCHOLIC ACID

The present invention discloses method for preparing deoxycholic acid (DCA) or an ester thereof or a pharmaceutically acceptable salt thereof. Said compounds may be applied to remove a fat deposition. 2. The method of claim 1 , wherein the hydrogenation condition in c) is pd/C as a catalyst and N-Methylpyrrolidone as a solvent.3. The method of claim 1 , wherein the condition of the carbonyl reduction and deprotection in d) is dissolving the compound 1.5 in tetrahydrofuran claim 1 , dropwise adding LiAl (OtBu) H at −5 to 5° C. claim 1 , stirring at room temperature claim 1 , and followed by dropwise adding p-toluenesulfonic acid.4. The method of claim 1 , wherein the dicarbene transfer reagent in f) is PhPCHCHBr claim 1 , KOtBu; the Lewis acid in g) is EtAlCl; the hydrogenation condition in h) comprises pd/C or PtOas a catalyst; the hydrogenation condition in i) comprises tert-butylhydroperoxide and pyridinium chlorochromate; the hydrogenation condition in j) comprises pd/C or PtOas a catalyst; the reducing agent in k) is LiAl(OtBu)H.5. The method of claim 1 , wherein the deprotection and the hydrolysis condition in 1) comprise reacting the compound 6 with an alkali metal hydroxide claim 1 , an alkali metal alcoholate claim 1 , an alkaline earth metal hydroxide claim 1 , an alkaline earth metal alcoholate claim 1 , or a mixture thereof6. The method of claim 5 , wherein the alkali metal hydroxide is NaOH.8. An intermediate compound selected from the group consisting of:(Z)-3α-benzoxy-5β-pregna-9 (11), 17 (20)-diene (1);(E)-3α-benzoxy-5β-cholo-9 (11), 16-diene-24-acid methyl ester(2);3α-benzoxy-5β-cholo-9(11)-alkene-24-acid methyl ester(3);3α-benzoxy-5β-cholo-9(11) -en-12-ketone-24-carboxylate(4);3α-benzoxy-5β-cholane-12-ketone-24-acid methyl ester(5);3α-benzoxy-5β-cholo-9(11) -en-12-hydroxy-24-acid methyl ester(5a);3α-benzoxy-5β-cholane-12β-hydroxy-24-acid methyl ester(5b);3α-benzoxy-5β-cholane-12α-hydroxy-24-acid methyl ester(6); and5β-androstane-9(11)-alkene-17-(1,3 ...

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 153-. (canceled)55. The compound of claim 54 , wherein the Rgroup is selected from the group consisting of H claim 54 , methyl claim 54 , and trifluoromethyl.56. The compound of claim 54 , wherein Ris selected from the group consisting of H claim 54 , methoxy claim 54 , ethoxy claim 54 , and an optionally substituted morpholinyl ring.57. The compound of claim 54 , wherein Ris H.58. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the alpha position.59. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the beta position.60. The compound of claim 54 , wherein each instance of - - - between C-Cis absent and Ris in the beta position.61. The compound of claim 54 , wherein Ris ═O claim 54 , methoxy or H.62. The compound of claim 54 , wherein Ris methyl.63. The compound of claim 54 , wherein Ris beta-methoxy.64. The compound of claim 54 , wherein Ris beta-spirooxirane.65. The compound of claim 54 , wherein Ris beta-cyano.66. The compound of claim 54 , wherein Ris ═O.67. The compound of claim 54 , wherein Ris beta-nitro.68. The compound of claim 54 , wherein Ris beta-CHC(O)—.69. The compound of claim 54 , wherein Ris beta-HOCHC(O)—.73. The method of claim 72 , wherein the disorder is selected from the group consisting of insomnia claim 72 , mood disorders claim 72 , convulsive disorders claim 72 , anxiety claim 72 , or symptoms of ethanol withdrawal. This application is a continuation application and claims priority to U.S. patent application Ser. No. 15/459,492, filed on Mar. 15, 2017, which claims ...

Small molecules active against gram-negative bacteria

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

OXYSTEROLS AND METHODS OF USE THEREOF

Compounds are provided according to Formula (I): 144-. (canceled)47. The method according to claim 46 , wherein the disorder is inflammatory bowel disease.48. The method according to claim 46 , wherein the disorder is diabetes.49. The method according to claim 46 , wherein the disorder is colitis.51. The method according to claim 50 , wherein the disorder is sterol synthesis disorder.52. The method according to claim 50 , wherein the disorder is a cognitive disorder.53. The method according to claim 50 , wherein the disorder is a mood disorder. This application is a Continuation Application of U.S. National Phase application Ser. No. 15/319,504 filed Dec. 16, 2016, which is a National Phase Application under 35 U.S.C. § 371 of International Application No. PCT/US2015/036510 filed Jun. 18, 2015, which claims priority to U.S. Provisional Application No. 62/014,014 filed Jun. 18, 2014, and U.S. Provisional Application No. 62/107,236 filed Jan. 23, 2015, the entire contents of which are incorporated herein by reference.NMDA receptors are heteromeric complexes comprised of NR1, NR2, and/or NR3 subunits and possess distinct recognition sites for exogenous and endogenous ligands. These recognition sites include binding sites for glycine, and glutamate agonists and modulators. NMDA receptors are expressed in the peripheral tissues and the CNS, where they are involved in excitatory synaptic transmission. Activating these receptors contributes to synaptic plasticity in some circumstances and excitotoxicity in others. These receptors are ligand-gated ion channels that admit Ca2+ after binding of the glutamate and glycine, and are fundamental to excitatory neurotransmission and normal CNS function. Positive modulators may be useful as therapeutic agents with potential clinical uses as cognitive enhancers and in the treatment of psychiatric disorders in which glutamatergic transmission is reduced or defective (see, e.g., Horak et al., J. of Neuroscience, 2004, 24(46), 10318- ...

19-NOR C3, 3-DISUBSTITUTED C21-C-BOUND HETEROARYL STEROIDS AND METHODS OF USE THEREOF

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 3. The method of claim 1 , wherein Ris —CH claim 1 , —CHCH claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHOCH claim 1 , or substituted or unsubstituted cyclopropyl.4. The method of claim 3 , wherein Ris —CH.5. The method of claim 1 , wherein Ris —OH claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCHCHCH claim 1 , —CH claim 1 , —CHCH claim 1 , —CHCHCH claim 1 , substituted or unsubstituted cyclopropyl claim 1 , fluoro claim 1 , or chloro.6. The method of claim 1 , wherein Ris H.7. The method of claim 1 , wherein Rand Rare both hydrogen.8. The method of claim 1 , wherein Rand Rare joined to form ═O (oxo).9. The method of claim 1 , wherein represents a double bond claim 1 , and Ris hydrogen claim 1 , fluoro claim 1 , —CH claim 1 , or —CF.10. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare hydrogen.11. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare —CHor —CF.12. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare fluoro.13. The method of claim 1 , wherein represents a single bond claim 1 , and Ris substituted or unsubstituted Calkyl claim 1 , or halogen claim 1 , and Ris hydrogen.14. The method of claim 13 , wherein Ris fluoro.15. The method of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen.16. The method of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris substituted or unsubstituted Calkyl claim 1 , —COR claim 1 , —C(═O)R claim 1 , —CN claim 1 , —NO claim 1 , or halogen claim 1 , wherein Ris substituted or unsubstituted Calkyl.17. The method of claim 16 , wherein at least one of R claim 16 , R claim 16 , R claim 16 , R claim 16 , and Ris substituted or unsubstituted —CH.18. The method of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen.22. A method ...

Intermediates for the Synthesis of Bile Acid Derivatives, in Particular of Obeticholic Acid

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Methods for assembly of tetracyclic compounds by stereoselective c9-c10 bond formation

The present disclosure relates to stereodefined polycyclic (e.g., tetracyclic) compounds that contain quaternary centers at one or multiple ring fusions, synthetic methods for preparing such compounds, and methods of using such compounds to treat a disease, such as a brain tumor and, particularly, a glioma.

SYNTHESIS OF ENT-PROGESTERONE AND INTERMEDIATES THEREOF

The present invention relates to the synthesis of ent-progesterone and intermediates thereof. 6. The method for preparing ent-progesterone according to claim 5 , wherein R is —OTs claim 5 , —OMs claim 5 , —OTf claim 5 , —Cl claim 5 , —Br claim 5 , or —I.8. The method for preparing ent-progesterone according to claim 7 , wherein the reaction step comprises a reductive silylation followed by de-silylation and methylation.15. The method for preparing ent-progesterone according to claim 14 , wherein R is —OTs claim 14 , —OMs claim 14 , —OTf claim 14 , —Cl claim 14 , —Br claim 14 , or —I.21. A method for preparing ent-progesterone comprising the step of reacting an enone intermediate compound with triethylsilane and a catalyst to form a silyl enol ether.22. The method for preparing ent-progesterone according to claim 1 , wherein said method has fewer than 17 linear steps.23. The method for preparing ent-progesterone according to claim 1 , wherein said method has fewer than 15 linear steps.24. The method for preparing ent-progesterone according to claim 1 , wherein said method has fewer than 13 linear steps.25. The method for preparing ent-progesterone according to claim 1 , wherein said method has fewer than 12 linear steps.26. The method for preparing ent-progesterone according to claim 2 , wherein said method has fewer than 17 linear steps.27. The method for preparing ent-progesterone according to claim 2 , wherein said method has fewer than 15 linear steps.28. The method for preparing ent-progesterone according to claim 2 , wherein said method has fewer than 13 linear steps.29. The method for preparing ent-progesterone according to claim 2 , wherein said method has fewer than 12 linear steps.30. The method for preparing ent-progesterone according to claim 3 , wherein said method has fewer than 17 linear steps.31. The method for preparing ent-progesterone according to claim 3 , wherein said method has fewer than 15 linear steps.32. The method for preparing ent- ...

MICRORNA MODULATORS AND METHOD FOR IDENTIFYING AND USING THE SAME

The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent and determining whether the test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.

Neuroactive steroids, compositions, and uses thereof

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R 1 , R 2 , R 3 , and R 4 are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

NOVEL PROCESS FOR PREPARATION OF CORTICOSTEROIDS

The present invention discloses a process for the preparation of pregnadiene derivatives having formula I, their stereoisomer and intermediate thereof. Formula I wherein each substituent is independently, Rand Ris hydrogen or C-Cstraight, branched alkyl chain, saturated or unsaturated cycloalkyl; Ris hydrogen or wherein Rrepresents C-Cstraight, branched alkyl chain or cycloalkyl; Ris hydrogen or halogen; Ris hydrogen or halogen; 3. The process as claimed in claim 1 , wherein the compound of Formula (1) isi. (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;ii. 6α,9-difluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione, cyclic 16,17-acetal with acetone,21-acetate;iii. 1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;iv. ((16,17-(butylidenebis(oxy))-11,21-dihydroxy-, (11-β,16-α)-pregna-1,4-diene-3,20-dionev. 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9, 13-dimethyl-16-oxo-5, 7-dioxapentacyclo [10.8.0.02,9.04, 8.013,18] icosa-14, 17-dien-8-yl]-2-oxoethyl 2-methylpropanoate.vi. (1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-onevii. (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS)-4b-fluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2′,1′:4,5]indeno[1,2-d][1,3]dioxol-2-oneviii. 2-[(1S,2S,4R,8S,9S,11S,12R,13S)-12′-fluoro-11′-hydroxy-9′,13′-dimethyl-16′-oxo-5′,7′-dioxaspiro[cyclopentane-1,6′ pentacyclo[10.8.0.02,9.04,8.013,18]icosane]-14′,17′-dien-8′-yl]-2-oxoethyl acetate;ix. (11β,16α)-9-Fluoro-11,16,17,21-tetrahydroxypregna-1,4-diene-3,20-dione;x. (11β,16α)-21-(3,3-Dimethyl-1-oxobutoxy)-9-fluoro-11-hydroxy-16,17-((1-methylethylidene)bis(oxy))pregna-1,4-diene-3,20-dione4. The ...

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The compound of claim 1 , wherein one or both of Ror R claim 1 , when present and other than H claim 1 , are in the beta configuration.3. The compound of or claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.4. The compound of one of the preceding claims claim 1 , wherein Ris selected from the group consisting of H claim 1 , methoxy claim 1 , ethoxy claim 1 , and an optionally substituted morpholinyl ring.5. The compound of one of the preceding claims claim 1 , wherein Ris H.6. The compound of one of the preceding claims claim 1 , wherein Ris substituted methyl.7. The compound of one of the preceding claims claim 1 , wherein the C—H is in the alpha position.8. The compound of one of preceding - claim 1 , wherein the C—H is in the beta configuration and Rgroup is in the beta configuration.9. The compound of one of the preceding claims claim 1 , wherein Ris H.10. The compound of one of the preceding claims claim 1 , wherein Ris ═O claim 1 , methoxy or H.11. The compound of one of the preceding claims claim 1 , wherein Ris methyl.13. The compound of wherein Ris methyl.14. The compound of or claim 12 , wherein Ris beta-methoxy.15. The compound of or claim 12 , wherein Ris beta-spirooxirane.16. The compound of or claim 12 , wherein Ris beta-cyano.17. The compound of or claim 12 , wherein Ris ═O.18. The compound of or claim 12 , wherein Ris beta-nitro.19. The compound of or claim 12 , wherein Ris beta-CHC(O)—.20. The compound of or claim 12 , wherein Ris beta-HOCHC(O)—.22. The compound of claim 21 , wherein Ris methyl.23. A ...

Synthesis of a substituted indene derivative

This invention is directed to methods of preparing AQX-1125 having the formula: This invention is also directed to intermediates utilized in the methods of preparing AQX-1125.

GUGGULPHOSPHOLIPID METHODS AND COMPOSITIONS

The present invention relates to the methods for preparing synthetic guggulphospholipids, their fatty acid analogues and other bioactive molecules. The present invention relates to E-guggulsterone and Z-guggulsterone or mixture of E- and Z-guggulsterones, and E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols synthetically modified to guggulphospholipids and analogues and salts thereof, fatty acid analogues of guggulsterols, guggulsulfate and salts thereof, guggulphosphate and salts thereof; and guggulsterols conjugated with drugs for use as prodrugs. Also the present invention provides a novel method for the preparation of E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols from a mixture of E- and Z-guggulsterones. The present invention further relates to guggulphospholipids and other bioactive molecules incorporated into complexes such as liposomes, complexes, emulsions, vesicles, micelles, and mixed micelles, which can include other active agents, such as hydrophobic or hydrophilic drugs for use, e.g., in treatment of human and animal diseases. 4. The method of claim 3 , wherein said guggulsterone I is an E-isomer or Z-isomer or a mixture of E and Z isomers.5. The method of claim 2 , wherein said guggulsterol IIA is an E-isomer or Z-isomer claim 2 , or a mixture of E- and Z-isomer.6. The method of claim 2 , wherein said guggulsterol is optically pure claim 2 , and wherein said guggulsterol is a mixture of optical isomers.7. A method of preparing guggulsterol IIA claim 2 , comprising treating guggulsterone I in one of more steps to produce preparing guggulsterol IIA.8. A method of preparing a compound of formula IV claim 2 , V claim 2 , VI claim 2 , VIII claim 2 , IX or X of claim 2 , claim 2 , or claim 2 , wherein at least one step comprises the use of a phosphoramidite reagent or a phosphorylating agent.9. The method of claim 8 , wherein said phosphoramidite reagent is selected from the group consisting of NN- ...

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus. 237-. (canceled)39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.40. The method of or wherein the compound is administered orally claim 38 , subcutaneously claim 38 , intravenously claim 38 , or intramuscularly.41. The method of or wherein the compound is administered chronically. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane.Neurotransmitters are stored in presynaptic vesicles and are released under the ...

Neuroactive steroids and methods of use thereof

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1 , R 2 , R 3a , R 3b , R 4 , R 5a , R 5b , R 6a , and R 6b are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of CNS-related conditions.

Neuroactive enantiomeric 15-, 16- and 17-substituted steroids as modulators for gaba type-a receptors

The present disclosure is generally directed to neuroactive enantiomeric 15-, 16- and 17-substituted steroids with additional optional substituents at carbons 3, 4, 6, 7, 10 and 13, and pharmaceutically acceptable salts thereof, for use as, for example, modulators for GABA type-A receptors. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

19-nor c3, 3-disubstituted c21-n-pyrazolyl steroids and methods of use thereof

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein , R 1 , R 2 , R 3a , R 3b , R 4a , R 4b , R 5 , R 6 , and R 7 are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

Neuroactive steroids, compositions, and uses thereof

Described herein are steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R 1 , R 2a , R 2b , R 3 , R 4 , R 5a , R 5b , R 6 , and Z are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The method of claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.3. The method of claim 1 , wherein Ris ═O claim 1 , methoxy or H.4. The method of claim 1 , wherein Ris beta-cyano.6. The method of claim 1 , wherein{'sub': 1', '1', '4', '1', '4', '1', '4, 'Ris selected from (C-Calkyl)-O, spirooxirane, cyano, ═O, (C-Calkyl)C(O), and HO(C-Calkyl)C(O).'}7. The method of claim 1 , wherein the mood disorder is selected from the group consisting of depression claim 1 , dysthymic disorder claim 1 , and bipolar disorder. This application is divisional of U.S. patent application Ser. No. 15/586,853 filed on May 4, 2017, which is a divisional of U.S. patent application Ser. No. 14/652,717 filed on Jun. 16, 2015 (now U.S. Pat. No. 9,676,812), which is a U.S. National Stage Application based on International Patent Application No. PCT/US2013/076214 filed on Dec. 18, 2013, which claims priority benefit of U.S. Provisional Patent Application Ser. No. 61/738,822 filed on Dec. 18, 2012, the entire contents of which are incorporated herein by reference.The invention was made with government support under GM047969, awarded by the National Institutes of Health. The government has certain rights in the invention.The present disclosure is generally directed to novel compounds having utility as an anesthetic and/or in the treatment of disorders relating to GABA function and activity. More specifically, the present disclosure is directed to steroids having a 19-alkoxy-17-substituted tetracyclic structure that are neuroactive and suitable for use ...

Compositions and methods for treating cns disorders

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein , A, R 1 , R 2 , and R 3 are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use, e.g., for treating a subject suffering from a disease or disorder described herein.

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Described herein are neuro-active steroids of the Formula (I): (I) or a pharmaceutically acceptable salt thereof; wherein R, R, R, G, X, Y, Z, and n are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia. 166-. (canceled)68. The method of claim 67 , wherein Ris C-Calkyl.69. The method of claim 68 , wherein Ris —CH claim 68 , —CHCH claim 68 , or —CH(CH).70. The method of claim 67 , wherein Ris C-Calkyl.71. The method of claim 70 , wherein Ris —CH.72. The method of claim 67 , wherein each of Rand Ris independently —H or -D.73. The method of claim 67 , wherein each of Rand Ris independently —H.74. The method of claim 67 , wherein one of Rand Ris —H claim 67 , -D claim 67 , or C-Calkyl claim 67 , and the other of Rand Ris —H.76. The method of claim 75 , wherein X is N claim 75 , and Y and Z are CH.77. The method of claim 75 , wherein X and Z are N claim 75 , and Y is CH.78. The method of claim 75 , wherein X claim 75 , Y claim 75 , and Z are N.79. The method of claim 75 , wherein Ris C-Calkyl.80. The method of claim 75 , wherein Ris C-Calkyl.81. The method of claim 75 , wherein each of Rand Ris independently —H or -D.82. The method of claim 75 , wherein one of Rand Ris —H claim 75 , -D claim 75 , or C-Calkyl claim 75 , and the other of Rand Ris —H.83. The method of claim 75 , wherein one of Rand Ris -D or C-Calkyl claim 75 , and the other of Rand Ris —H.84. The method of claim 75 , wherein n is 1.85. The method of claim 75 , wherein Ris C-Calkyl or C-Calkoxy.86. The method of claim 75 , wherein Ris —S(O)R claim 75 , —NRR claim 75 , —C(O)R claim 75 , or —C(O)OR.87. The method of claim 75 , wherein Ris halogen.88. The method of claim 75 , wherein n is 1 or 2 claim 75 , and Ris cyano claim 75 , halogen claim 75 , nitro claim 75 , or C-Calkoxy.91. The ...

STABLE TOPICAL PHAMACEUTICAL COMPOSITIONS OF HALOBETASOL PROPIONATE

The present invention provides a stable topical pharmaceutical composition of halobetasol propionate. The present invention discloses an impurity of compound of Formula II and its process of preparation. It also relates to a method of evaluating stability of a topical pharmaceutical composition of halobetasol propionate. 2. The compound of Formula II of claim 1 , wherein R is ethyl.4. The process for the preparation of claim 3 , wherein the compound of Formula II claim 3 , wherein R is ethyl.5. The process for the preparation of claim 3 , wherein the non-aqueous solvent is selected from the group consisting of methyl alcohol claim 3 , ethyl alcohol claim 3 , isopropyl alcohol claim 3 , n-propyl alcohol claim 3 , isobutyl alcohol claim 3 , n-butyl alcohol claim 3 , or mixtures thereof.6. The process for the preparation of claim 5 , wherein the non-aqueous solvent is ethyl alcohol.8. The stable topical pharmaceutical composition of claim 7 , wherein the compound of Formula II claim 7 , wherein R is ethyl.10. The stable topical pharmaceutical composition of claim 9 , wherein the compound of Formula II claim 9 , wherein R is ethyl.11. The stable topical pharmaceutical composition of claim 9 , wherein the non-aqueous solvent is selected from the group consisting of methyl alcohol claim 9 , ethyl alcohol claim 9 , isopropyl alcohol claim 9 , n-propyl alcohol claim 9 , isobutyl alcohol claim 9 , n-butyl alcohol claim 9 , or mixtures thereof.12. The stable topical pharmaceutical composition of claim 11 , wherein the non-aqueous solvent is ethyl alcohol.13. The stable topical pharmaceutical composition of claim 9 , wherein the non-aqueous solvent is present in an amount of 10% w/w to about 60% w/w based on the total weight of the composition.14. The stable topical pharmaceutical composition of claim 9 , wherein the halobetasol propionate is present from about 0.01% w/w to about 0.5% w/w based on the total weight of the composition.15. The stable topical pharmaceutical ...

PREPARATION OF BILE ACIDS AND INTERMEDIATES THEREOF

Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided. 2. The composition of claim 1 , further comprising a solvent.3. The composition of claim 1 , wherein the hydrogenation catalyst comprises Pd/C.4. The composition of claim 2 , wherein the solvent is DMF.7. The composition of claim 6 , further comprising a solvent.8. The composition of claim 6 , wherein the olefination reagent is PhPCHCHBr.11. The composition of claim 10 , wherein the composition further comprises a solvent.12. The composition of claim 10 , wherein —OP is —OAc and —COR is —COMe.14. The composition of claim 13 , further comprising a solvent.15. The composition of claim 13 , wherein the hydrogenation catalyst comprises Pd/C or PtO.16. The composition of claim 13 , wherein —OP is —OAc and —COR is —COMe.18. The composition of claim 17 , wherein the composition further comprises a solvent.19. The composition of claim 17 , wherein the reducing agent is lithium tri-tert-butoxyaluminum hydride.20. The composition of claim 17 , wherein —OP is —OAc and —COR is —COMe. This application is a divisional of U.S. patent application Ser. No. 13/752,175, filed Jan. 28, 2013; which is a continuation of U.S. patent application Ser. No. 13/010,727, filed Jan. 20, 2011, issued as U.S. Pat. No. 8,362,285; which is a divisional of U.S. patent application Ser. No. 12/613,969, filed Nov. 6, 2009, issued as U.S. Pat. No. 7,994,351 on Aug. 9, 2011; which is a continuation of U.S. patent application Ser. No. 12/153,446, filed May 16, 2008, issued as U.S. Pat. No. 7,902,387 on Feb. 16, 2011; which claims the benefit under 35 U.S.C. 119(a) of United Kingdom Application Serial No. 0807615.0, filed Apr. 25, 2008; each of which are hereby incorporated by reference into this application in their entirety.1. Field of the InventionThe present invention relates to the synthesis of deoxycholoic acid and pharmaceutically acceptable salts and intermediates thereof.2. State of the ArtRapid removal of body ...

DEHYDROGENATION CATALYST, AND CARBONYL COMPOUND AND HYDROGEN PRODUCTION METHOD USING SAID CATALYST

Objects of the present invention are to provide a novel dehydrogenation reaction catalyst, to provide a method that can produce a ketone, an aldehyde, and a carboxylic acid with high efficiency from an alcohol, and to provide a method for efficiently producing hydrogen from an alcohol, formic acid, or a formate, and they are accomplished by a catalyst containing an organometallic compound of Formula (1). 2. The method according to claim 1 , wherein the oxygen-containing compound is an alcohol.3. The method according to claim 1 , wherein the oxygen-containing compound is formic acid or a formate.4. The method according to any one of to claim 1 , wherein L is an aquo ligand.5. The method according to any one of to claim 1 , wherein Ar is an optionally substituted cyclopentadienyl group claim 1 , and M is iridium.6. A dehydrogenation catalyst comprising an organometallic compound of Formula (1) claim 1 , wherein it is for use in the method according to any one of to .7. A method for producing a carbonyl compound claim 1 , wherein an alcohol is dehydrogenated by use of the dehydrogenation method according to any one of to to produce a corresponding carbonyl compound.8. The method according to claim 7 , wherein the carbonyl compound is a ketone or an aldehyde.9. The method according to claim 7 , wherein the alcohol is a primary alcohol claim 7 , the carbonyl compound is a carboxylic acid claim 7 , and a solvent comprising water is used.10. A method for producing hydrogen claim 7 , wherein hydrogen is prepared by dehydrogenation of an alcohol claim 7 , a mixture containing an alcohol and water claim 7 , formic acid claim 7 , or a formate using the dehydrogenation method according to any one of to .12. The organometallic compound according to claim 11 , wherein Ar is an optionally substituted cyclopentadienyl group claim 11 , and M is iridium.14. The organometallic compound according to claim 13 , wherein Ar is an optionally substituted cyclopentadienyl group claim 13 , ...

Intermediates for the Synthesis of Bile Acid Derivatives, in Particular of Obeticholic Acid

The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease.

NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Compounds are provided according to Formula (I): 2. The compound of claim 1 , wherein Ris unsubstituted Calkyl.3. The compound of claim 2 , wherein Ris —CH claim 2 , —CHCH claim 2 , or —CHCHCH.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Rand Rare both hydrogen.6. The compound of claim 1 , wherein Ris hydrogen.7. The compound of claim 1 , wherein Rand Rare both hydrogen.8. The compound of claim 1 , wherein at least one of Rand Ris fluorine.9. The compound of claim 1 , wherein Ris a non-hydrogen group substituted with fluorine.10. The compound of claim 1 , wherein Ris a non-hydrogen group substituted with one or more —ORgroups claim 1 , wherein Ris hydrogen or substituted or unsubstitued alkyl.11. The compound of claim 1 , wherein Ris a substituted or unsubstituted Calkyl claim 1 , substituted or unsubstituted Calkenyl claim 1 , substituted or unsubstituted Calkynyl claim 1 , or substituted or unsubstituted Ccarbocyclyl.12. The compound of claim 1 , wherein Ris hydrogen.13. The compound of claim 1 , wherein Ris —CHor —CF.14. The compound of claim 1 , wherein Ris —CFand Ris hydrogen or Calkyl.15. The compound of claim 1 , wherein Ris a non-hydrogen group substituted with fluorine claim 1 , and Ris —CH.16. The compound of claim 15 , wherein Ris substituted with one or more —ORgroups claim 15 , wherein Ris hydrogen or substituted or unsubstitued alkyl.17. The compound of claim 1 , wherein Ris a substituted or unsubstituted Calkyl claim 1 , substituted or unsubstituted Calkenyl claim 1 , substituted or unsubstituted Calkynyl claim 1 , or substituted or unsubstituted Ccarbocyclyl claim 1 , and Ris —CH.18. The compound of claim 1 , wherein Ris Calkyl claim 1 , Ris a non-hydrogen group substituted with fluorine claim 1 , and Ris —CH.19. The compound of claim 1 , wherein Ris Calkyl claim 1 , Ris a non-hydrogen group substituted with fluorine claim 1 , and Ris hydrogen.20. The compound of claim 1 , wherein Ris Calkyl claim 1 , Ris a ...

Compositions and methods for treating cns disorders

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein , A, R 1 , R 2 , and R 3 are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use, e.g., for treating a subject suffering from a disease or disorder described herein.

METHODS FOR THE PURIFICATION OF DEOXYCHOLIC ACID

Synthetic methods for preparing deoxycholic acid and intermediates thereof, high purity synthetic deoxycholic acid, compositions and methods of use are provided. Also, provided are processes for the synthesis of 12-keto or 12-α-hydroxysteroids from Δ-9,11-ene, 11-keto or 11-hydroxy-β-steroids. This invention is also directed to novel compounds prepared during the synthesis. This invention is also directed to the synthesis of deoxycholic acid starting from hydrocortisone. 116-. (canceled)2122.-. (canceled)24. The compound of claim 17 , wherein Rand Rtogether with the carbon atom attached thereto form a keto group.2664.-. (canceled)65. The compound of claim 17 , wherein R is hydrogen.67. The compound of claim 19 , wherein Rand Rtogether with the carbon atom attached thereto form a keto group.69. The compound of claim 19 , wherein R is hydrogen. This application is a continuation of U.S. patent application Ser. No. 14/532,940, filed Nov. 4, 2014, which is a continuation of U.S. patent application Ser. No. 13/140,421, filed Sep. 24, 2012, which is a U.S. national stage of PCT/US2010/061150, filed Dec. 17, 2010, which claims the benefit of U.S. provisional application Ser. No. 61/288,132, filed on 18 Dec. 2009, U.S. provisional application Ser. No. 61/61/302,007, filed on 5 Feb. 2010, U.S. provisional application Ser. No. 61/303,816, filed on 12 Feb. 2010, U.K. Application No. 1008726.0 filed on 25 May 2010, and U.S. provisional application Ser. No. 61/348,686, filed on 26 May 2010, all of which are incorporated by reference herein in their entirety.This invention is directed to the synthesis of deoxycholic acid and salts thereof as well as to intermediates useful in the synthesis of deoxycholic acid. In one embodiment, this invention provides synthetic methods for preparing deoxycholic acid or a salt thereof starting from hydrocortisone. This invention is also directed to intermediates such as 12-keto or 12-α-hydroxysteroids as well as novel processes for their ...

PREPARATION OF BILE ACIDS AND INTERMEDIATES THEREOF

Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided. 120.-. (canceled)22. The method of claim 21 , wherein the hydrogenation conditions of part (a) comprise a PtOcatalyst.23. The method of claim 21 , wherein the oxidizing agent of part (b) is CrO.24. The method of claim 21 , wherein the hydrogenation conditions of part (c) comprise a Pd/C catalyst.25. The method of claim 21 , wherein the hydrogenation conditions of part (c) comprise a PtOcatalyst.26. The method of claim 21 , wherein the reducing agent of part (d) is LiAl(OtBu)H.27. The method of claim 21 , wherein P is —C(O)CH.28. The method of claim 27 , wherein the deprotection and hydrolysis conditions of part (e) comprise reacting compound 2.1 with an alkali earth alkoxide claim 27 , an alkali metal hydroxide claim 27 , or a mixture of both.29. The method of claim 27 , wherein the deprotection and hydrolysis conditions of part (e) comprise reacting compound 2.1 with LiOH.30. The method of claim 21 , wherein R is CH. This application is a continuation of U.S. patent application Ser. No. 16/051,409, filed Jul. 31, 2018, pending, which is a divisional of U.S. patent application Ser. No. 14/696,204, filed Apr. 24, 2015, issued as U.S. Pat. No. 10,053,486 on Aug. 21, 2018, which is a divisional of U.S. patent application Ser. No. 13/752,175, filed Jan. 28, 2013; now abandoned, which is a continuation of U.S. patent application Ser. No. 13/010,727, filed Jan. 20, 2011, issued as U.S. Pat. No. 8,362,285; which is a divisional of U.S. patent application Ser. No. 12/613,969, filed Nov. 6, 2009, issued as U.S. Pat. No. 7,994,351 on Aug. 9, 2011; which is a continuation of U.S. patent application Ser. No. 12/153,446, filed May 16, 2008, issued as U.S. Pat. No. 7,902,387 on Feb. 16, 2011; which claims the benefit under 35 U.S.C. 119(a) of United Kingdom Application Serial No. 0807615.0, filed Apr. 25, 2008; each of which are hereby incorporated by reference into this application in their ...

Conjugated Neuroactive Steroid Compositions And Methods Of Use

The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject.

NEUROACTIVE 13, 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS

The present disclosure is generally directed to neuroactive 13, 17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein the C—H is in the alpha configuration.4. The compound of claim 1 , wherein Ris H or —OCH.5. The compound of claim 1 , wherein Ris H or —OCH.6. The compound of claim 1 , wherein Ris methyl or —CHOCH.7. The compound of claim 1 , wherein Ris H or —OCH.8. The compound of claim 1 , wherein Ris —CH═CHor —C(O)CH.9. The compound of claim 1 , wherein Ris selected from the group consisting of —CH═CH claim 1 , ethyl claim 1 , —C(O)CH claim 1 , hydroxy alkyl claim 1 , and haloalkyl.10. The compound of claim 9 , wherein Ris hydroxyl alkyl claim 9 , and further is selected from the group consisting of —C(OH)CHand —CH(OH).11. The compound of claim 9 , wherein Ris —CHCl.12. The compound of claim 1 , wherein Ris H.15. A pharmaceutically acceptable salt of a compound of .16. A pharmaceutical composition comprising a compound of claim 1 , a pharmaceutically acceptable salt thereof claim 1 , or a combination of two or more thereof claim 1 , and a pharmaceutically acceptable carrier. This application is a continuation application and claims priority benefit of U.S. patent application Ser. No. 14/191,740, filed on Feb. 27, 2014 and which claims priority benefit of U.S. Provisional Patent Application Ser. No. 61/771,350, filed on Mar. 1, 2013, the entire contents of which are incorporated herein by reference.This invention was made with government support under NIH Grant #GM47969, awarded by the National Institute of Health. The Government has certain rights in the invention.The present disclosure is generally directed to novel compounds ...

Process for the preparation of estetrol

The present invention relates to a process for the preparation of estra-1,3,5(10)-trien-3, 15a, 16a, 1713-tetraol (estetr-01), via a silyl enol ether derivative 17-B-oxy-3-A-oxy-estra-1,3,5(10), 16-tetraene, wherein A is a protecting group and B is —Si(R 2 ) 3 . The invention further relates to a process for the synthesis of 3-A-oxy-estra-1,3,5(10), 15-tetraen-17-one, in which A is a protecting group, via silyl enol ether derivative 17-B-oxy-3-A-oxy-estra-1,3,5(10),16-tetraene, and B is —Si(R 2 ) 3 .

Neuroactive steroids and compositions thereof

Provided herein is a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 5 , R 6a , R 6b , R 7a , R 7a , R 11a , R 11b , R 12a , R 12b , R 16a , R 16b , R 19 , R 11a , R 22 , R X , R Y and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

19-nor neuroactive steroids and methods of use thereof

Provided herein are 3,3-disubstituted19-nor-steroidal compounds according to Formula(I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions,for example, treatment of sleep disorders, mood disorders,schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders,personality disorders,autism spectrum disorders, pain,traumatic brain injury, vascular diseases,substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.

Process for the preparation of fusidic acid sodium salt

본 발명은 푸시딘산으로부터 이의 소디움염을 제조하는 방법에 관한 것으로, 더욱 상세하게는 푸시딘산을 단일 또는 혼합용매 중에서 소디움 2-에틸 헥사노에이트와 반응시켜 푸시딘산 소디움염을 고수율 및 고순도로 분리 제조하는 방법에 관한 것이다. FIELD OF THE INVENTION The present invention relates to a process for preparing its sodium salt from fusidic acid, more particularly by reacting fusidic acid with sodium 2-ethyl hexanoate in a single or mixed solvent to separate the fusidic acid sodium salt in high yield and high purity. It relates to a manufacturing method.

Patent JPH0212479B2

１７α−エチニル−１７β−ヒドロキシ−１８−メチル−４，１５−エストラジエン−３−オンの製造方法、及びこの方法の中間生成物

Process for producing steroid (16 alpha 17 beta)cyclohexane- or naphthalene-21-carboxylic acids or their esters

Steroids having the formula <IMAGE> wherein X is hydrogen or halogen; Y is hydrogen, methyl or fluorine; R4 is chlorine, fluorine or hydroxy and R5 is hydrogen or R4 and R5 together are = O; R2 and R3 are the same or different and are hydrogen, alkyl or aryl or taken together with the double bond to which they are attached form a benzene ring; R6 and R7 are the same or different and are hydrogen, alkyl, alkoxy, formyl, <IMAGE> phenyl or cyano and in addition hydroxy, halogen carboalkoxy and alkylcarbonyl when R2 and R3 are separate with the proviso that when R6 and R7 are different, one of R6 and R7 is hydrogen; R8 is hydrogen or CHR9R10 wherein R9 and R10 are the same or different and are hydrogen or alkyl may be used as intermediates in preparing compounds having antiinflammatory activity. The invention extends to acetals of the 21-aldehydes.

Neuroactive steroids, compositions and use thereof

FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula (I), in which A is selected from a group , , , and ; R 1 is -CH 3 , -CH 2 F, -CHF 2 , -CH 2 CH 3 , -CH 2 OCH 3 or -CH 2 OCH 2 CH 3 ; R 2 and R 3 is selected independently from -H, halogen, -CH 3 , -OCH 3 or -OCH 2 CH 3 ; R 4 is -CF 3 , cyano, -CH 3 , -C(O)OR a or -C(O)NR b R c ; R a is -H, or (C 1 -C 2 )alkyl; each R b and R c is independently H; and n is integer from 0 to 1; or when A is (A-3) or (A-5), R 1 is-CH 3 , -CH 2 F, -CH 2 OCN 3 or -CHF 2 , and n is equal to 0, then at least one of R 2 and R 3 is not H. Invention also relates to individual compounds, to a pharmaceutical composition, to a method of treating a CNS related disorder associated with GABA function, to a method of treating a seizure, to a method of treating epilepsy, to a method of treating epileptic status. H (I). EFFECT: technical result is obtaining novel compounds of formula (I), having properties of modulator GABA A , which can be useful in treating a CNS related disorder. 32 cl, 71 ex, 4 tbl, 22 dwg РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 699 359 C2 (51) МПК C07J 7/00 (2006.01) C07J 43/00 (2006.01) A61K 31/57 (2006.01) A61K 31/58 (2006.01) A61P 25/00 (2006.01) A61P 25/08 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61P 25/18 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61P 25/20 (2006.01) A61P 25/24 (2006.01) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07J 7/009 (2018.08); C07J 43/003 (2018.08); A61K 31/57 (2018.08); A61K 31/58 (2018.08); A61P 25/00 (2018.08); A61P 25/08 (2018.08); A61P 25/18 (2018.08); A61P 25/20 (2018.08); A61P 25/24 (2018.08) 2016151727, 29.05.2015 (24) Дата начала отсчета срока действия патента: 29.05.2015 Дата регистрации: (73) Патентообладатель(и): СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: 29.05.2014 CN PCT/CN2014/078820 (43) Дата публикации заявки: 02.07.2018 Бюл. № 19 (45) Опубликовано: 05.09.2019 Бюл. № 25 C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: ...

Method of preparing 16beta-methyl steroid, intermediates

FIELD: organic synthesis. SUBSTANCE: invention provides method of preparing 16beta-methyl steroid with formula I: 16β (I), which is distinguished by that compound of general formula II: (II), wherein cycles A and B form residue substituted by keto group in position 3 as in formula optionally protected by cyclic acetal- or thioacetal-type groups depicted by formulas , or with n=2 or 3, is treated with dehydration agent to give compound III: (III). The latter (preliminarily protected in case it bears free keto group) is affected by an organometallic methylation agent to give, after hydrolysis of intermediate imine, methyl ketone of formula IV: (IV), which is further treated with epoxidation agent in alkali medium to give compound of formula V: (V). 20-Keto group in compound V is then protected by a cyclic acetal-type group as above to form protected compound VI: (VI), which is treated with an organometallic methylation agent to give 16 beta-methyl derivative depicted by general formula VII: РДУ ПЧ ГЭ (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ "” 2451 774 ' 57 МК’ С 07 4 5/00 13) СЛ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95108877/04, 01.06.1995 (24) Дата начала действия патента: 01.06.1995 (30) Приоритет: 02.06.1994 ЕК 9406743 (46) Дата публикации: 21.06.2000 (56) Ссылки: МО 88103534, А, 1988. ЕР 054810, А, 1987. Ф.П.Тринус. Фармако-терапевтический справочник. - Киев, "Здоровья", 1989, с.263. (98) Адрес для переписки: 129010, Москва, ул. Большая Спасская 25, стр.3, ООО "Городисский и Партнеры", Лебедевой Н.Г. (71) Заявитель: РУССЕЛЬ ЮКЛАФ (ЕК) (72) Изобретатель: Жерт Катрин (ЕК), Вива Мишель (ЕК) (73) Патентообладатель: РУССЕЛЬ ЮКЛАФ (ЕК) (54) СПОСОБ ПОЛУЧЕНИЯ 16В-МЕТИЛЬНОГО СТЕРОИДА, ПРОМЕЖУТОЧНЫЕ ПРОДУКТЫ. (57) Реферат: Описывается способ — получения 16 В-метильного стероида формулы 1, отличающийся тем, что проводят обработку соединения общей формулы 1, в которой циклы А и В представляют собой остатск, в котором К ...

Method for producing derivatives of 19-norprogesterone

FIELD: progestative agent. SUBSTANCE: derivative of 19-norprogesterone has formula 1 where R 1 is H, methoxymethyl, tetrahydropyranyl, radical having formula 2, acyl C 1 -C 6 . Desired product yield is 14-88% , melting point is 76-237 C. 3-alkoxy-extra-1,3-triene is used as reagent 1, bromide of propyltriphenylphosphonium is used as reagent 2, 3-alkoxy-12- propylidenextra 1, 3, 3, (10) triene is used as reagent 3. Li in liquid NH 3 is used as reagent 4; 3-oxo-21-methyl-19-norpregnane 4,17(20)diene is used as reagent 5; trialkylorthoformiate together with acid are used as reagent 6; 3-alkoxy-17- propylidene-extra-3,5-diene is used as reagent 7; POCl+ dimethylformamide is used as reagent 8. 3-alkoxy-6-formyl-21- methyl-19-norpregnatriene-3,5,17 (20) is used as reagent 9; mixed hydride of alkali metal is used as reagent 10; 6-hydroxymethyl-21- methyl-3-oxo-19-norpregna-4,17 (20)-diene is used as reagent 11. Hydrochloric acid HCl is used as reagent 12; 21-methyl-6-methylene- 3-oxo-19-norpregna-4,17 (20)-diene is used as reagent 13; Pd/C+C 2 H 5 OH+CH 3 COONa is as reagent 14. 3-oxo-6-methylextra-4,6-diene is used as reagent 15. OSO+ N-oxidetriethylamine hydroxide are used as reagent 16, 17-hydroxy-6,21- dimethyl-3,20-dioxo-19-norpregna-4,6-diene is used as reagent 17. If it is necessary reaction is followed by methoxymethylation, dihydropiranylation or by acylation. Formulae 1 and 2 are given in specification. EFFECT: improves efficiency of the method. Эту 6б00Сс пы ГЭ РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ” 2009 146. 13) Сл С 07 + 9/00 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 4614494/04, 26.06.1989 (30) Приоритет: ЕК/27.10.87/8714806 (30) Приоритет: 27.10.1987 ЕК 87 8714806 (46) Дата публикации: 15.03.1994 (71) Заявитель: Лаборатуар Терамекс С.А. (МС) (72) Изобретатель: Ален Пласко[ЕН], Мохамед Нежиб НасрауиП М] (73) Патентообладатель: Лаборатуар Терамекс С.А. (МС) (54) СПОСОБ ПОЛУЧЕНИЯ ПРОИЗВОДНЫХ 19- ...

New preparation method of 16β-methyl steroids and novel intermediates thereof

본 발명은, 다음 일반식(Ⅱ)의 시안하이드린으로부터 다음 일반식(I)의 베타메타손을 제조하는 방법과 신규한 중간체에 관한 것이다. 상기 식에서, 고리 A및 B는 다음의 잔기를 나타낸다. 여기에서, K는 옥소 라디칼 도는 옥소 라디칼의 보호기를 나타내고, R 1 은 에테르 또는 에스테르 잔기를 나타낸다.

Neurostimulatory steroids, compositions, and their use

Neuroactive 19-alkoxy-17-substituted steroids and methods of treatment using same

FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I-g) or a pharmaceutically acceptable salt thereof, where Rchosen from (C-Calkyl)-O, spirooxirane, cyano, =O, nitro, (C-Calkyl)C(O) and HO(C-Calkyl)C(O); Ris H; Ris H; Ris methyl; Ris H; - - - is an optional additional C-C bond providing a C=C bond between C-C, provided that, if present, Ris not =O or spirooxirane. Invention also relates to individual compounds, a method for inducing anesthesia, to a method for treating disorders associated with the GABA function..EFFECT: technical result: obtaining novel compounds of formula (I-g), which can be useful in the treatment of disorders associated with the GABA function.11 cl, 5 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07J 1/00 (2006.01) C07J 5/00 (2006.01) C07J 7/00 (2006.01) C07J 9/00 (2006.01) C07J 13/00 (2006.01) C07J 21/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА C07J 41/00 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61K 31/56 (2006.01) A61K 31/566 (2006.01) A61K 31/57 (2006.01) (12) (13) 2 663 665 C2 A61K 31/575 (2006.01) A61K 31/58 (2006.01) A61P 23/00 (2006.01) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК (21)(22) Заявка: 2015129546, 18.12.2013 (24) Дата начала отсчета срока действия патента: (73) Патентообладатель(и): ВАШИНГТОН ЮНИВЕРСИТИ (US), СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) Дата регистрации: 08.08.2018 Приоритет(ы): (30) Конвенционный приоритет: (56) Список документов, цитированных в отчете о поиске: Jan-Ake Gustafsson et al. "Steroid 18.12.2012 US 61/738,822 (45) Опубликовано: 08.08.2018 Бюл. № 22 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 20.07.2015 R U 2 6 6 3 6 6 5 (86) Заявка PCT: US 2013/076214 (18.12.2013) (87) Публикация заявки PCT: WO 2014/100228 (26.06.2014) Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" (54) НЕЙРОАКТИВНЫЕ 19-АЛКОКСИ-17-ЗАМЕЩЕННЫЕ СТЕРОИДЫ И СПОСОБЫ ЛЕЧЕНИЯ С ИХ ПРИМЕНЕНИЕМ (57) Реферат: Изобретение относится к соединению H; - - - означает ...

Derivatives of 19-nor progesterone; process for producing them and the pharmaceutical compositions incorporating them

내용 없음. No content.

Neuroactive 19-alkoxy-17-substituted steroids, prodrugs thereof, and methods of treatment using same

본 개시내용은 일반적으로, 예를 들어 마취제로서 및/또는 GABA 기능 및 활성과 관련된 장애의 치료에서 사용하기 위한 본원에 언급된 바와 같은 신경활성 19-알콕시-17-치환된 스테로이드 및 그의 제약상 허용되는 염에 관한 것이다. 본 개시내용은 추가로 이러한 화합물을 포함하는 제약 조성물에 관한 것이다. The present disclosure generally relates to neuroactive 19-alkoxy-17-substituted steroids and pharmaceutically acceptable thereof as mentioned herein, for example, for use as an anesthetic and / or for the treatment of disorders associated with GABA function and activity. It is about salt becoming. The present disclosure further relates to pharmaceutical compositions comprising such compounds.

19-nor c3, 3-disubstituted c21-n-pyrazolyl steroids and methods of use thereof

FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I),is a single or double bond; Ris Calkyl optionally substituted with Calkoxy or one to two halogen groups; Ris hydrogen, unsubstituted Calkyl or -OR, where Ris an unsubstituted Calkyl; Ris hydrogen and Ris hydrogen; each of Rand Rin each case independently represent hydrogen or halogen, provided that ifbetween Cand Cis a simple bond, then hydrogen in position Cand substituent R, each independently, is represented in an alpha or beta configuration, and Ris absent; each of R, Rand Rin each case independently represent hydrogen, halogen, -NO, -CN, -C(=O)R, -C(=O)OR, -SR, -S(=O)R, -S(=O)R, -S(=O)ORor Calkyl, optionally substituted with halogen; Rin each case independently represents unsubstituted Calkyl; and where at least one of R, Rand Rindependently represents halogen, -NO, -CN, -C(=O)R, -C(=O)OR, -SR, -S(O)R, -S(=O)R, -S(=O)ORor Calkyl, optionally substituted with halogen, where Ris an unsubstituted Calkyl. Invention also relates to pharmaceutical compositions and to individual compounds..EFFECT: technical result: novel compounds of formula (I) having properties of a GABA modulator.46 cl, 52 dwg, 5 tbl, 71 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 675 855 C2 (51) МПК C07J 7/00 (2006.01) C07J 43/00 (2006.01) A61K 31/58 (2006.01) A61P 25/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07J 7/00 (2006.01); C07J 43/003 (2006.01); A61K 31/58 (2006.01); A61P 25/00 (2006.01) (21)(22) Заявка: 2015149008, 17.04.2014 (24) Дата начала отсчета срока действия патента: Дата регистрации: 25.12.2018 17.04.2013 CN PCT/CN2013/074323 (43) Дата публикации заявки: 22.05.2017 Бюл. № (56) Список документов, цитированных в отчете о поиске: WO 9805337 A1, 12.02.1998. US 5939545 A, 17.08.2018. RU 2194712 C2, 20.12.2002. RU 2243232 C2, 27.12.2004. WO 9521617 A1, 17.08.1995. 15 (45) Опубликовано: ...

Method for purification of fusidic acid

본 발명은 푸시딘산의 정제방법에 관한 것으로, 더욱 상세하게는, 푸시딘산 조생성물 용액내의 pH를 2 내지 3으로 조절한 뒤, 수지상에 적용하여 푸시딘산을 선택적으로 흡착시키고, 이를 유기 극성용매를 적용시켜 용출분리시키는 공정을 포함하는 푸시딘산의 정제방법에 관한 것이다. 이러한 본 발명에 따르면, 푸시딘산을 99% 이상의 고순도로 정제할 수 있어 약효를 월등히 높이고, 불순물에 의한 부작용을 방지할 수 있을 뿐만 아니라, 수출을 가능하게 하여 경제적으로도 매우 우수한 효과가 있음을 알 수 있었다. 또한, 본 발명에서 사용되는 흡착 수지는 100% 메탄올과 증류수를 이용하여 반복 세척하여 재사용할 수 있으므로 보다 경제적임을 알 수 있다. The present invention relates to a method for purifying fusidic acid, and more particularly, after adjusting the pH in the crude product of fusidic acid to 2-3, it is applied to the resin to selectively adsorb the fusidic acid, and the organic polar solvent is adsorbed. It relates to a method for purifying fusidic acid comprising the step of applying and eluting separation. According to the present invention, it is possible to purify the fusidic acid with a high purity of 99% or more to significantly increase the drug efficacy, to prevent side effects caused by impurities, and also to export it is found to have a very good economic effect. Could. In addition, it can be seen that the adsorption resin used in the present invention is more economical because it can be reused by repeated washing with 100% methanol and distilled water.

Method of obtaining epoxyandrostanes

Neuroactive steroids, compositions and use thereof

FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I), in which A is 5-member heteroaryl with 2–4 nitrogen atoms, 5,6-bicyclic heteroaryl with 2–4 nitrogen atoms or 6-member heterocyclyl with 2 heteroatoms independently selected from nitrogen and oxygen, where A is attached through nitrogen and optionally substituted with 1–4 substitutes, each of which is independently selected from cyano, halogen, C-C-alkyl, C-C-halogenalkyl, C-C-alkoxy, -OC-C-halogenalkyl, -C(O)R, -C(O)ORand -S(O)2R; each Ra is C-C-alkyl; L is -C (R)(R) -; Ris hydrogen or C-Calkyl; Ris hydrogen, C-Calkyl or C-Chaloalkyl; each Ris hydrogen; Ris hydrogen; andis a single bond. Invention also relates to use of compound of formula (I).(I).EFFECT: technical result is obtaining novel compounds of formula (I), having modulating GABA activity.38 cl, 3 tbl, 92 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (51) МПК C07J 43/00 A61K 31/57 A61K 31/58 A61P 23/00 A61P 25/08 (11) (13) 2 696 585 C2 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07J 43/003 (2013.01); A61K 31/57 (2013.01); A61K 31/58 (2013.01) (21)(22) Заявка: 2016110418, 22.08.2014 (24) Дата начала отсчета срока действия патента: Дата регистрации: 05.08.2019 (73) Патентообладатель(и): СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) 23.08.2013 US 61/869,440; 23.08.2013 US 61/869,446; 18.06.2014 US 62/014,018 (43) Дата публикации заявки: 26.09.2017 Бюл. № 27 (45) Опубликовано: 05.08.2019 Бюл. № 22 (56) Список документов, цитированных в отчете о поиске: RU 2243232 C2, 27.12.2004. WO 9521617 A1, 17.08.1995. WO 9805337 A1, 12.02.1998. WO 2013056181 A1, 18.04.2013. RU 2194712 C2, 20.12.2002. C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 23.03.2016 (86) Заявка PCT: US 2014/052417 (22.08.2014) 2 6 9 6 5 8 5 (87) Публикация заявки PCT: R U 2 6 9 6 5 8 5 Приоритет(ы): (30) Конвенционный приоритет: R U 22.08.2014 (72) Автор(ы): МАРТИНЕС БОТЕЛЬЯ ...

19-nor c3,3-disubstituted c21-n-pyrazolyl steroids and methods of use thereof

본원은 하기 화학식 I의 19-노르 C3,3-이치환된 C21-피라졸릴 스테로이드 및 그의 제약상 허용되는 염을 제공한다: <화학식 I> (상기 화학식에서, R 1 , R 2 , R 3a , R 3b , R 4a , R 4b , R 5 , R 6 및 R 7 은 본원에서 정의된 바와 같음). 상기 화합물은 각종 CNS-관련 상태의 예방 및 치료, 예를 들면 수면 장애, 기분 장애, 정신분열증 스펙트럼 장애, 경련성 장애, 기억 및/또는 인지 장애, 운동 장애, 인격 장애, 자폐증 스펙트럼 장애, 통증, 외상성 뇌손상, 혈관 질환, 약물 남용 장애 및/또는 금단 증후군 및 이명의 치료에 유용하다. Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula I and pharmaceutically acceptable salts thereof: <Formula I> (In the above formula, R 1 , R 2 , R 3a , R 3b , R 4a , R 4b , R 5 , R 6 and R 7 are as defined herein). The compounds are used for the prevention and treatment of various CNS-related conditions, for example sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, memory and/or cognitive disorders, motor disorders, personality disorders, autism spectrum disorders, pain, traumatic It is useful for the treatment of brain injury, vascular disease, substance abuse disorder and/or withdrawal syndrome and tinnitus.

19-nor neurostimulatory steroids and methods of use thereof

Androstein derivatives having a quaternary ammonium group substituted at the 16-position, pharmaceutical compositions containing the same, and methods for preparing the same

본 발명은 신경근 차단효과를 가지는 신규한, 치료학적으로 활성의 안드로스테인에 관한 것으로, 16-위치에 사차 암모늄기가 치환되고, 그들을 함유하는 제약학적인 조성물, 그들을 생산하기 위한 방법, 및 제조를 위한 신규한 중간체이다.

Process for preparing 4,1720-prostadien-3,16-dione from 4-androsten-3,17-dione and the intermediate compounds for preparing the same

본 발명은 4-안드로스텐-3,17-디온으로부터 인간의 저밀도 지방단백질(LDL; low density lipoprotein) 및 콜레스테롤 수치를 효과적으로 낮추고, 고밀도 지방단백질(HDL; high density lipoprotein)을 높이는 일반식(VI)으로 표시되는 4,17(20)- E -프로스타디엔-3,16-디온( E -Guggulesterone; E -구굴스테론) 및 일반식(VII)로 표시되는 4,17(20)- Z -프로스타디엔-3,16-디온( Z -Guggulesterone; Z -구굴스테론)의 제조방법을 제공한다. The present invention effectively lowers human low density lipoprotein (LDL) and cholesterol levels from 4-androsten-3,17-dione, and formula (VI) to increase high density lipoprotein (HDL). E - - prostasin -3,16- dione 4,17-diene (20) represented by (E -Guggulesterone; E - gugul stacking theory) 4,17 (20) and represented by the general formula (VII) - Z - Provided is a method for preparing prostadiene-3,16-dione ( Z- Guggulesterone; Z -Gugulsterone). 또한, 본 발명은 화합물 (VI)과 (VII)을 제조하기 위한 중간체인 상기 일반식(III), (V), (VIII) 및 (IX)를 합성하는 방법을 제공한다. The present invention also provides a method for synthesizing the above general formulas (III), (V), (VIII) and (IX), which are intermediates for the preparation of compounds (VI) and (VII).

19-nor neuroactive steroids and methods of using them

FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I) is a single or double bond, as valence allows; A has formula (A-1) or formula (A-2), where attachment point is in G 1 or G 2 in formula (A-1) and attachment point is in G 2 or G 3 in formula (A-2); G 1 is N, NR N1 or CR G1 , as valence allows; G 2 is N or -C=N-, as valence allows; G 3 is N or CR G3 , as valence allows; G 4 is N or CR G4 , as valence allows; G 5 is N or CR G5 , as valence allows; G 6 is N or CR G6 , as valence allows; and G 7 is N or CR G7 , as valence allows; in each case R G1 , R G2 , R G3 , R G4 , R G5 , R G6 and R G7 independently represents hydrogen, halogen, -CN, -OR GA or unsubstituted C 1-6 alkyl; in each case R N1 is unsubstituted C 1-6 alkyl; in each case R GA independently represents hydrogen, C 1-6 alkyl substituted with fluorine or unsubstituted C 1-6 alkyl; R 1 is C 1-6 alkyl substituted with fluorine, methoxy or ethoxy, or unsubstituted C 1-6 alkyl; R 2 is hydrogen; R 3a is hydrogen and R 3b is hydrogen; each R 4a or R 4b independently represents hydrogen; provided that if the bond p is a double bond, then the bond q is a single bond, provided that if the bond q is a double bond, then the bond p is a single bond and R 4b is absent; and provided that both bonds q and p are single bonds, hydrogen in C5 is in alpha or beta configuration. Invention also refers to pharmaceutical salts of compounds, to a pharmaceutical composition, to individual compounds and their pharmaceutically acceptable salts. , (A-1), (A-2). EFFECT: obtaining novel compounds of formula (I), having the GABA modulator property. 21 cl, 13 dwg, 3 tbl, 95 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 700 264 C2 (51) МПК C07J 43/00 (2006.01) A61K 31/58 (2006.01) A61P 25/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07J 43/003 (2016.08); A61K 31/58 (2016.08); A61P 25/00 (2019. ...

Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid

The invention relates to compounds of general formula (I): wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease.

Process and intermediates for the 6,7-alpha-epoxidation of steroid 4,6-dienes

The invention relates to a process for preparing a compound of general formula (Ia): wherein R 2 , Y, R 4 and R 5 are as defined herein, wherein the epoxidation is conducted using an oxidant and methyltrioxorhenium as a catalyst (MeReO3). The invention also relates to certain compounds per se. The compounds are intermediates in the synthesis of synthetic bile acids.

Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid

The present invention relates to compounds which are intermediates in the synthesis of bile acid derivatives with pharmacological activity. The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease. In addition, the invention relates to a method of synthesizing these intermediates and a method of preparing obeticholic acid and obeticholic acid analogues from the compounds of the invention.

Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid

The invention relates to compounds of general formula (I): wherein: , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Y are as defined herein. The compounds are intermediates in the synthesis of synthetic bile acids which are useful in the treatment of conditions such as liver disease.

Production of 9(11)-dehydrosteroid

Process for the preparation of estetrol

The present invention relates to a process for the preparation of estra-1,3,5(10)-trien-3,15α,16α,17β-tetraol (estetrol), via a silyl enol ether derivative 17-B-oxy-3-A-oxy-estra-1,3,5(10),16-tetraene, wherein A is a protecting group and B is ―Si(R 2 ) 3 . The invention further relates to a process for the synthesis of 3-A-oxy-estra-1,3,5(10),15-tetraen-17-one, wherein A is a protecting group, via said silyl enol ether derivative.

19-NOR NEUROACTIVE STEROIDS AND WAYS OF THEIR APPLICATION

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2019 126 333 A (51) МПК C07J 43/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2019126333, 17.04.2014 (71) Заявитель(и): СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 08.10.2019 Бюл. № 28 (72) Автор(ы): БОТЕЛЛА, Габриэль Мартинез (US), ХАРРИСОН, Бойд Л. (US), РОБИШО, Альбер, Жан (US), САЛИТУРО, Франческо Дж. (US), БЕРЕЗИС, Ричард Томас (CN) (54) 19-НОР НЕЙРОАКТИВНЫЕ СТЕРОИДЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ A или его фармацевтически приемлемая соль; где представляет собой одинарную или двойную связь, как позволяет валентность; A имеет формулу (A-1) или формулу (A-2) R U 2 0 1 9 1 2 6 3 3 3 A (57) Формула изобретения 1. Соединение формулы (I) 2 0 1 9 1 2 6 3 3 3 Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" R U 17.04.2013 CN PCT/CN2013/074312 (62) Номер и дата подачи первоначальной заявки, из которой данная заявка выделена: 2015149009 16.11.2015 (A-1) или (A-2), где точка присоединения находится в G1 или G2 в формуле (A-1) и точка Стр.: 1 присоединения находится в G2 или G3 в формуле (A-2); G1 представляет собой N, NRN1, O, S, C или C-RG1, как позволяет валентность; G2 представляет собой N, NRN2, O, S, C, -C=N- или C-RG2, как позволяет валентность; G3 представляет собой N, NRN3, O, S, C или C-RG3, как позволяет валентность; G4 представляет собой N, NRN4, C-RG4или C-(RG4)2, как позволяет валентность; G5 представляет собой N, NRN5, C-RG5 или C-(RG5)2, как позволяет валентность; G6 представляет собой N, NRN6, C-RG6 или C-(RG6)2, как позволяет валентность; и G7 представляет собой N, NRN7, C-RG7 или C-(RG7)2, как позволяет валентность; в каждом случае RG1, RG2, RG3, RG4, RG5, RG6, и RG7 независимо представляет собой водород, галоген, -NO2, -CN, -ORGA, -N(RGA)2, -C(=O)RGA, -C(=O)ORGA, -OC(=O)RGA, -OC(=O)ORGA, -C(=O)N(RGA)2, -N(RGA)C(=O)RGA, -OC(=O)N(RGA)2, ...

Derivatives of 11,21-bisphenyl-19-norpregnane, method of their synthesis, pharmaceutical composition and method of its preparing

FIELD: organic chemistry, steroids, pharmacy. SUBSTANCE: invention relates to derivatives of 11,21-bisphenyl-19-norpregnane of the formula (I) where R 1 means H, halogen atom, NR 5 R 6 being R 5 and R 6 mean independently hydrogen atom or C 1-6 -alkyl; R 2 is hydrogen atom; R 1 and R 2 are in common C 1-3 -alkylenedihydroxy-group optionally substituted with one or some halogen atoms; R 3 means methyl; R 4 means C(O)-NR 5 R 6 , SO n C 1-6 -alkyl optionally substituted with one or some halogen atoms, SO n -C 3-6 -cycloalkyl, SO 2 -NR 5 R 6 , 2-hydroxypyrrolidinyl or NR 5 R 6 where R 5 and R 6 are independently hydrogen atom, C 1-6 -alkyl, or R 5 and R 6 in common form C 3-6 -alkylene; n = 1 or 2; R 7 means H or C 1-7 -alkyl; R 8 means H; X means H, OH, O or NOH, or to their pharmaceutically acceptable salts. Compounds show antiglucocor-ticoid activity and can be used for treatment or prophylaxis of patients with glucocorticoid-depending diseases. Invention describes also method of synthesis of compounds of the formula (I). EFFECT: improved method of synthesis, valuable curative properties. 9 cl, 2 tbl, 14 ex сУ6бссЬс ПЧ сэ РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК? ВИ” 2152 952‘ 13) С2 С 07 4 5/00, А 61 К 31/56 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 95107892/04, 18.05.1995 (24) Дата начала действия патента: 18.05.1995 (30) Приоритет: 19.05.1994 ЕР 94201431.7 (46) Дата публикации: 20.07.2000 (56) Ссылки: 4$ 4544555, 1985. Тринус Ф.П. Фармакотерапевтический справочник. - Киев: "Здоровья", 1989, с.261-264. (98) Адрес для переписки: 129010, Москва, ул. Большая Спасская 25, стр.3, ООО "Городисский и Партнеры", Лебедевой Н.Г. (71) Заявитель: АКЦО НОБЕЛЬ Н.В. (№) (72) Изобретатель: Гебхар Рональд (М1), Ван Дер Ворт Хендрикус Адрианус Антониус (МЫ) (73) Патентообладатель: АКЦО НОБЕЛЬ Н.В. (№) (54) ПРОИЗВОДНЫЕ 11,21-БИСФЕНИЛ-19-НОРПРЕГНАНА, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЕЕ ПОЛУЧЕНИЯ 57 ...

Derivatives of androstane substituted at 16-position with quaternary ammonium group, pharmaceutical composition

Изобретение относится к новым производным андростана формулы I, где R 1 - атом водорода или алкaноил: R 2 - алканоил; W 1 и W 2 - одинаковые или различные или один из символов означает химическую связь, а другой - , или W 1 - , а W 2 - ; один из R 3 и R 4 - атом водорода, а другой - OR 1 или R 3 и R 4 вместе означают оксогруппу или C 2-5 - алкилендиоксил; Е, R 5 - алкил или алкенил; при условии, что в производных, содержащих циклическую структуру с двумя атомами азота, только тот заместитель Е означает указанную выше группу, который соединен химической связью с атомом азота, непосредственно не связанным со стероидным скелетом молекулы, в то время как другой заместитель Е означает свободную пару электронов; X - - анион, n и m независимо друг от друга - 2 или 4 при условии, что сумма n и m в одной циклической структуре равна от 4 до 6 независимо от их значения в другом цикле. Соединения формулы I обладают неразрушающим нервно-мышечным блокирующим действием и могут использоваться для миорелаксации во время эндотрахеальной анестезии, а также при проведении шоковой терапии и для лечения спастических заболеваний поперечно-полосатых мышц. 2 с. и 1 з. п. ф-лы, 4 табл. ЕСОтСТс ПЧ Го РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (19) (51) МПК ВИ” 2 124 021 Сл С 07 3 43/00, А 61 К 31/56 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 93049598/04, 29.10.1993 (30) Приоритет: 02.11.1992 НУ Р 9203436 (46) Дата публикации: 27.12.1998 (56) Ссылки: 1. СВ, 1138605, 1971. 2. 4.Мед.Свет, 16, 116 (1973). 3. ЕР, 0008824, 1971. 4. ЕР, 0208497, 1987. 5. ЕР, 0330253, 1989. 6. ЕР, 0288102, 1987. Г. М.С. Вомтап. Рпагт/ о! пеиготис!аг Гипсйоп. р. 99-105, 1980. 8. НЦ 172287. 9. ФУР, 59-7120, 1984. 10. (Ц, 1389681, 1988. 11. Машковский М.Д., "Лекарственные средства", М., Медицина, 1978, 1, с. 201-285. (71) Заявитель: Рихтер Гедеон Ведьесети Дьяр РТ (НЦ) (72) Изобретатель: Золтан Туба (НЦ), Сильвестер Е.Визи (НЦ), Ференц Ф.Фолдес (НУ), Шандор Махо (НЦ) (73) ...

Compositions and methods for treating cns disorders

FIELD: medicine; pharmaceuticals. SUBSTANCE: invention relates to a compound of formula (I-a), in which ring A is 5-member or 9-member heteroaryl containing 2–4 nitrogen atoms; where ring A is attached through a nitrogen atom; R 1 denotes unsubstituted C 1-3 alkyl or alkoxyC 1-6 alkyl; R 2 is hydrogen; R 3a is hydrogen and R 3b is hydrogen; R 4a is hydrogen; R 6 is unsubstituted C 1-6 alkyl, hydroxyC 1-6 alkyl, haloC 1-6 alkyl, halogen, cyano, nitro, OR A6 , C(=O)OR A6 , N(R C6 )(R D6 ), C(=O)N(R C6 )(R D6 ) or N(R C6 )C(=O)R A6 ; n has value 1; R A6 represents hydrogen or unsubstituted C 1-6 alkyl and each of R C6 and R D6 independently represents hydrogen or unsubstituted C 1-6 alkyl; R 5 denotes hydrogen; each of R 7a and R 7b independently represents hydrogen and represents a simple bond. Invention also relates to individual compounds, a pharmaceutical composition, a method of treating convulsions, a method of treating epilepsy, a method of treating a CNS-related disorder. (I-a). EFFECT: obtaining novel compounds of formula (I-a), having properties of GABA modulators. 38 cl, 3 tbl, 161 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 733 756 C2 (51) МПК C07J 7/00 (2006.01) C07J 43/00 (2006.01) A61K 31/57 (2006.01) A61K 31/58 (2006.01) A61P 25/08 (2006.01) A61P 25/18 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА A61P 25/20 (2006.01) ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ A61P 25/28 (2006.01) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК C07J 7/00 (2019.02); C07J 43/003 (2019.02); A61K 31/57 (2019.02); A61K 31/58 (2019.02); A61P 25/08 (2019.02); A61P 25/18 (2019.02); A61P 25/20 (2019.02); A61P 25/28 (2019.02) (21)(22) Заявка: 2017116732, 16.10.2015 16.10.2015 Дата регистрации: 06.10.2020 Приоритет(ы): (30) Конвенционный приоритет: 16.10.2014 US 62/064,961 (43) Дата публикации заявки: 16.11.2018 Бюл. № 32 (45) Опубликовано: 06.10.2020 Бюл. № 28 (86) Заявка PCT: C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 16.05.2017 (56) Список документов, цитированных в отчете о ...

NEUROACTIVE STEROIDS, COMPOSITIONS AND THEIR APPLICATION

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2015 143 463 A (51) МПК G01N 33/566 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2015143463, 13.03.2014 (71) Заявитель(и): СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: 13.03.2013 US 61/780,671 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 13.10.2015 R U (43) Дата публикации заявки: 19.04.2017 Бюл. № 11 (72) Автор(ы): РЕДДИ Киран (US), ДОУЭРТИ Джеймс (US) (86) Заявка PCT: (87) Публикация заявки PCT: WO 2014/160441 (02.10.2014) R U (54) НЕЙРОАКТИВНЫЕ СТЕРОИДЫ, КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ (57) Формула изобретения 1. Способ оценки или лечения пациента, например пациента с описанным здесь нарушением, включающий: a) необязательно получение образца пациента; b) получение оценки и/или оценку образца на изменение в уровне 24(S)гидроксихолестерина по сравнению со стандартным образцом. 2. Способ по п. 1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества 24(S)-гидроксихолестерина или структурно родственного стерина или стероида, оксистерина, агониста NMDAR или позитивного аллостерического модулятора (PAM) NMDAR, или описанного здесь соединения, такого как соединение формулы (I). 3. Способ по п. 1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества антагониста NMDAR или негативного аллостерического модулятора (NAM) NMDAR. 4. Способ по п. 1, дополнительно включающий введение пациенту (например, в ответ на оценку образца) эффективного количества соединения, которое дополняет (например повышает) эндогенную активность или количество 24(s)-гидроксихолестерина (например соединения, ингибирующего фермент, который метаболизирует 24(s)-гидроксихолестерин (например соединения, ингибирующего 24-гидроксихолестерин-7-альфа-гидроксилазу (CYP39))). Стр.: 1 A 2 0 1 5 1 4 3 4 6 3 A Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3 ...

Processes and intermediates for 6,7-alpha-epoxidation of steroid 4,6-dienes

본 발명은, 산화제 및 촉매로서 메틸트리옥소레늄(MeReO3)을 사용하여 에폭시화를 수행하는, R 2 , Y, R 4 , 및 R 5 가 본 명세서에 정의된 바와 같은 일반식 (Ia)의 화합물의 제조 공정에 관한 것이다. 본 발명은 또한 소정의 화합물 그 자체에 관한 것이다. 화합물은 합성 담즙산의 합성에서의 중간체이다.

Patent RU2015143463A3

ВИ“? 2015143463” АЗ Дата публикации: 19.03.2018 Форма № 18 ИЗ,ПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение ж 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2015143463/15(067136) 13.03.2014 РСТЛО52014/026633 13.03.2014 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 61/780,671 13.03.2013 05 Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) НЕЙРОАКТИВНЫЕ СТЕРОИДЫ, КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЕ Заявитель: СЕЙДЖ ТЕРАПЬЮТИКС, ИНК., 0$ 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. п см. Примечания [ ] приняты во внимание следующие пункты: р [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) СОМ 33/566 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) СО1М 33/566, СО1М 33/53 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): ЕАРАТЬ, Езрасепе, боое, МСВТ, РАТЕМТСОРЕ, Рабеагсв, РИБМеча, КУРТО, ъслепсе Эиесь ИЗРТО, БД "Российская медицина", БД ВИНИТИ, РМЖ 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) ...

Method of producing fusidine acid derivatives or salts thereof

16 alpha-methylation

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Process for the preparation of hydrocortisone and intermediates

본 발명은 하기 일반식(I)의 히드로코르티손의 신규 제조 방법 및 신규 중간체에 관한 것이다. The present invention relates to novel processes for the preparation of hydrocortisone of the general formula (I) and novel intermediates.

NEUROACTIVE STEROIDS, COMPOSITIONS AND THEIR APPLICATIONS

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2019 126 637 A (51) МПК C07J 7/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ 2019126637, 29.05.2015 (21)(22) Заявка: (71) Заявитель(и): СЕЙДЖ ТЕРАПЬЮТИКС, ИНК. (US) Приоритет(ы): (30) Конвенционный приоритет: (43) Дата публикации заявки: 03.10.2019 Бюл. № 28 (72) Автор(ы): БОТЕЛЛА, Габриэль Мартинез (US), ХАРРИСОН, Бойд Л. (US), РОБИШО, Альбер Жан (US), САЛИТУРО, Франческо Дж. (US), БЕРЕЗИС, Ричард Томас (CN) (54) НЕЙРОАКТИВНЫЕ СТЕРОИДЫ, КОМПОЗИЦИИ И ИХ ПРИМЕНЕНИЯ R U (I) A 2 0 1 9 1 2 6 6 3 7 A (57) Формула изобретения 1. Соединение формулы (I) 2 0 1 9 1 2 6 6 3 7 Адрес для переписки: 129090, Москва, ул. Б.Спасская, 25, строение 3, ООО "Юридическая фирма Городисский и Партнеры" R U 29.05.2014 CN PCT/CN2014/078820 (62) Номер и дата подачи первоначальной заявки, из которой данная заявка выделена: 2016151727 28.12.2016 или его фармацевтически приемлемая соль; где в указанной формуле А выбирают из группы , , , и ; R1 представляет собой (C1-C6)галогеналкил или (C1-C6)алкил; R2 и R3 выбирают независимо из H, галогена, (C1-C6)алкила или алкокси; Стр.: 1 R4 представляет собой галоген, циано, нитро, -S(O)xRa, -NRbRc, (C1-C6)алкил, (C1-C6)алкокси, -C(O)Ra, -C(O)ORa или -C(O)NRbRc; Ra представляет собой H, арил, гетероарил или (C1-C6)алкил; каждый Rb и Rc представляет собой независимо H, -S(O)xRa, -C(O)Ra, (C1-C6)алкил или (C1-C6)алкокси, или Rb и Rc, взятые вместе с атомом, к которому они присоединены, образуют цикл; n равен целому числу от 0 до 2; и x равен целому числу от 0 до 2; где когда A представляет собой (A-1) или (A-2), тогда R1 выбирают из -CHF2, -CH2F, -CCl3, -CHCl2, -CH2Cl, -CBr3, -CHBr2, -CH2Br или (C1-C6)алкила; или когда A представляет собой (A-3) или (A-5), R1 представляет собой -CН3, -CH2F, A 2 0 1 9 1 2 6 6 3 7 6. Соединение по п.1, где соединение формулы (I) выбирают из соединения формулы (Ib) A R U 2 0 1 9 1 2 6 6 3 7 (Iа). R U -CH2ОCН3 или -CHF2, и n равен 0, тогда по ...

Method of producing derivatives of 5-androstene-17-one

Neuroactive steroids, compositions, and uses thereof

Process of producing 9-hydroxy-3-oxo-4,17(20)-pregnadiene-20-carboxylic acid

The subject invention concerns a novel one-stage fermentation process for making the useful steroid intermediate 9-hydroxy-3-oxo-4,17(20)-pregnadiene-20-carboxylic acid (I). This process is significantly superior to the best prior art process known for making (I).

PROCESS FOR PREPARING 16 ALPHA-SUBSTITUT PREGNANES

Patent FR2318174B1

DERIVATIVES OF ALLOPREGNANOLONE AND EPIALLOPREGNANOLONE AND USES THEREOF FOR TREATING A NEUROPATHOLOGICAL CONDITION

The present invention relates to novel neurosteroids, especially derivatives of allopregnanolone and of epiallopregnanolone of formula (I) and the uses thereof as medicament for the treatment of neuropathologies, in particular neuropathies induced by the chemotherapy of a cancer. These molecules according to the invention have both preventative and curative effects. The neurosteroids according to the invention may also be of use in the treatment of neurodegenerative disorders, in particular for preventing neuronal cell death. They may thus be used as neuroprotectants and/or as an agent that stimulates neuronal proliferation.

NOVEL 19-NOR PROGESTERONE DERIVATIVES, PROCESS FOR OBTAINING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

13-alkyl-3,11,17,20,21-pentaoxygenated-18,19- - dinorpregnenes and derivs

Neuroactive steroids, compositions, and uses thereof