NZ738847B2 - Oxysterols and methods of use thereof - Google Patents
Oxysterols and methods of use thereof Download PDFInfo
- Publication number
- NZ738847B2 NZ738847B2 NZ738847A NZ73884716A NZ738847B2 NZ 738847 B2 NZ738847 B2 NZ 738847B2 NZ 738847 A NZ738847 A NZ 738847A NZ 73884716 A NZ73884716 A NZ 73884716A NZ 738847 B2 NZ738847 B2 NZ 738847B2
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- NZ
- New Zealand
- Prior art keywords
- compound
- disorder
- acceptable salt
- pharmaceutically acceptable
- iii
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
Compounds are provided according to Formula (I): Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R1, R2, R3, R6, R7, R8, and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
Claims (43)
1. A compound of Formula (III): (III) or a pharmaceutically acceptable salt thereof, wherein: R1 is C1-6 alkyl; each of R2 and R3 is independently hydrogen, n, C1-6 alkyl, or carbocyclyl; or R2 and R3, together with the carbon atom to which they are attached, form a 3-8 membered ring; and R6 is hydrogen; wherein each C1-6 alkyl is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, -CN, -NO2, -OH, - C1-6 alkoxy, and -NH2; and wherein each carbocyclyl and 3-8 ed ring is independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, -CN, -NO2, - OH, -C1-6 alkoxy, -C1-6 alkyl, and -NH2.
2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl, -CHF2, -CF3, -CH2OCH3, -CH2OCH2CH3, ethyl, or isopropyl.
3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl or ethyl.
4. The nd of claim 1, or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is ndently hydrogen, C1-6 alkyl, or carbocyclyl; or R2 and R3, together with the carbon atom to which they are ed, form a 3-8 membered ring.
5. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein the 3-8 membered ring is a carbocyclyl ring.
6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein the carbocyclyl ring is cyclopropyl.
7. The nd of claim 4, or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is independently hydrogen, C1-6 alkyl, or carbocyclyl.
8. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is independently hydrogen, methyl, -CF3, ethyl, 3, propyl, isopropyl, ropyl, or butyl.
9. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen, methyl, -CF3, or ethyl.
10. The compound of claim 7, or a ceutically acceptable salt thereof, wherein R3 is methyl, -CF3, ethyl, -CH2CF3, propyl, isopropyl, cyclopropyl, or butyl.
11. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen and R3 is C1-6 alkyl.
12. The compound of claim 7, or a ceutically acceptable salt thereof, n R2 is C1- 3 is C 6 alkyl and R 1-6 alkyl.
13. The nd of claim 1, wherein the compound of Formula (III) is a compound of Formula (III-A) or Formula (III-B): (III-A) or (III-B), or a pharmaceutically acceptable salt f.
14. The compound of claim 13, wherein the compound of Formula (III-B) is a compound of Formula (III-C) or Formula (III-D): (III-C) or (III-D), or a pharmaceutically acceptable salt thereof.
15. The compound of claim 13, wherein the compound of Formula (III-A) is a compound of Formula ) or Formula (III-F): (III-E) or ), or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1, wherein the compound of Formula (III) is a compound of Formula (III-A-i-a) or a (III-B-i-a): (III-A-i-a) or (III-B-i-a), or a ceutically acceptable salt thereof.
17. The compound of claim 1, wherein the compound is selected from: or .
18. The compound of claim 1, wherein the compound is a pharmaceutically acceptable salt of: or .
19. The compound of claim 1, wherein the compound is selected from: , , , , , , , , , , , , , , or
20. The compound of claim 19, wherein the compound is:
21. The compound of claim 19, n the compound is:
22. The compound of claim 19, wherein the compound is:
23. The compound of claim 1, wherein the compound is a pharmaceutically acceptable salt of: , , , , , , , , , , , , , , or
24. The compound of claim 23, n the compound is a pharmaceutically acceptable salt
25. The compound of claim 23, wherein the compound is a pharmaceutically acceptable salt
26. The compound of claim 23, wherein the compound is a pharmaceutically acceptable salt
27. A pharmaceutical composition comprising a nd of any one of claims 1-17 and 19- 22, and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the pharmaceutically acceptable salt of any one of claims 1-16, 18, and 23-26, and a pharmaceutically acceptable carrier.
29. Use of a compound or pharmaceutically acceptable salt of any one of claims 1-26, or a pharmaceutical composition of claim 27 or 28, in the manufacture of a medicament for inducing sedation or anesthesia.
30. Use of a compound or pharmaceutically acceptable salt of any one of claims 1-26, or a pharmaceutical composition of claim 27 or 28, in the manufacture of a medicament for treating or preventing a disorder.
31. The use of claim 30, wherein the disorder is a intestinal (GI) disorder, a structural disorder ing the GI tract, an anal disorder, colon polyps, cancer, s, diabetes, a sterol synthesis disorder, or a metabolic er.
32. The use of claim 31, wherein the disorder is a GI disorder, n the GI disorder is inflammatory bowel disease.
33. The use of claim 31, wherein the er is cancer, diabetes, or a sterol synthesis disorder.
34. The use of claim 31, wherein the disorder is cancer.
35. The use of claim 31, wherein the disorder is a metabolic disorder.
36. Use of a compound or pharmaceutically acceptable salt of any one of claims 1-26, or a pharmaceutical composition of claim 27 or 28, in the manufacture of a medicament for treating or preventing a CNS-related condition.
37. The use of claim 36, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating disorder, a mood disorder, a psychotic er, a sleep er, a substance-related disorder, a personality er, an autism spectrum disorder, a neurodevelopmental disorder, multiple sclerosis, a sterol synthesis disorders, pain, an encephalopathy secondary to a medical condition, seizure disorder, stroke, traumatic brain injury, a movement er, vision ment, hearing loss, or tinnitus.
38. The use of claim 37, wherein the lated condition is a sterol synthesis disorder.
39. The use of claim 37, wherein the CNS-related condition is a tic disorder, wherein the psychotic disorder is schizophrenia.
40. The use of claim 37, wherein the CNS-related condition is an autism spectrum disorder.
41. The use of claim 36, wherein the CNS-related condition is Huntington’s disease or Parkinson’s disease.
42. The use of claim 36, wherein the CNS-related condition is Alzheimer’s disease.
43. The use of claim 37, wherein the CNS-related condition is an encephalopathy ary to a medical ion, wherein the encephalopathy secondary to a medical condition is anti- NMDA receptor encephalitis. Sage Therapeutics, Inc. By the Attorneys for the Applicant SPRUSON & FERGUSON
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ777726A NZ777726B2 (en) | 2016-07-06 | Oxysterols and methods of use thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562189048P | 2015-07-06 | 2015-07-06 | |
| US201662280394P | 2016-01-19 | 2016-01-19 | |
| PCT/US2016/041168 WO2017007836A1 (en) | 2015-07-06 | 2016-07-06 | Oxysterols and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ738847A NZ738847A (en) | 2024-05-31 |
| NZ738847B2 true NZ738847B2 (en) | 2024-09-03 |
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