NZ777726B2 - Oxysterols and methods of use thereof - Google Patents
Oxysterols and methods of use thereof Download PDFInfo
- Publication number
- NZ777726B2 NZ777726B2 NZ777726A NZ77772616A NZ777726B2 NZ 777726 B2 NZ777726 B2 NZ 777726B2 NZ 777726 A NZ777726 A NZ 777726A NZ 77772616 A NZ77772616 A NZ 77772616A NZ 777726 B2 NZ777726 B2 NZ 777726B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- disorder
- acceptable salt
- pharmaceutically acceptable
- alkyl
- Prior art date
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Classifications
-
- 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 (45)
1. A compound of Formula (II-B): (II-B) or a ceutically acceptable salt thereof, wherein: R1 is C1-6 alkyl; and each of R2 and R3 is ndently 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; 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 membered ring is independently optionally substituted with 1-5 substituents independently selected from the group ting 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 compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is independently hydrogen, C1-6 alkyl, or carbocyclyl, or wherein R2 and R3, taken er with the carbon atom to which they are attached, form a 3-8 ed ring.
5. The compound of claim 4, or a ceutically acceptable salt thereof, wherein the 3-8 membered ring is a carbocyclyl ring .
6. The compound of claim 5, or a pharmaceutically able salt thereof, wherein the carbocyclyl ring is cyclopropyl.
7. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein each of R2 and R3 is ndently 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 ndently hydrogen, methyl, -CF3, ethyl, -CH2CF3, propyl, isopropyl, cyclopropyl, or butyl.
9. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R2 is en, methyl, -CF3, or ethyl.
10. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein R3 is methyl, -CF3, ethyl, -CH2CF3, propyl, isopropyl, ropyl, 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 pharmaceutically acceptable salt thereof, wherein R2 is C1-6 alkyl and R3 is C1-6 alkyl.
13. The compound of claim 1, wherein the nd of Formula (II-B) is a compound of Formula (II-B-i) or Formula (II-B-ii): (II-B-i) (II-B- or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (II-B-iii): (II-B-iii), or a ceutically acceptable salt thereof.
15. The compound of claim 1, wherein the compound is:
16. The compound of claim 1, wherein the compound is a ceutically acceptable salt
17. The compound of claim 1, wherein the compound is selected from: , , , , , , , , , , , , , , , , , , , , or
18. The compound of claim 17, n the compound is selected from: , , , , , , , , , or .
19. The compound of claim 18, n the compound is:
20. The compound of claim 18, wherein the compound is:
21. The compound of claim 18, wherein the compound is:
22. The compound of claim 18, wherein the compound is:
23. The compound of claim 1, n the compound is a pharmaceutically acceptable salt , , , , , , , , , , , , , , , , , , , , or
24. The compound of claim 23, n the compound is a pharmaceutically acceptable salt , , , , , , , , , or .
25. The compound of claim 24, wherein the compound is a pharmaceutically acceptable salt
26. The compound of claim 24, wherein the nd is a pharmaceutically acceptable salt
27. The compound of claim 24, wherein the compound is a pharmaceutically acceptable salt
28. The compound of claim 24, wherein the compound is a pharmaceutically acceptable salt
29. A pharmaceutical composition comprising a compound of any one of claims 1-15 and 17- 22 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising a pharmaceutically able salt of any one of claims 1-14, 16, and 23-28, and a pharmaceutically able carrier.
31. Use of a compound or pharmaceutically acceptable salt of any one of claims 1-28, or a pharmaceutical composition of claim 29 or 30, in the manufacture of a medicament for inducing sedation or anesthesia.
32. Use of a compound or ceutically acceptable salt of any one of claims 1-28, or a pharmaceutical composition of claim 29 or 30, in the manufacture of a medicament for treating or preventing a disorder.
33. The use of claim 32, wherein the disorder is a gastrointestinal (GI) disorder, a structural disorder ing the GI tract, an anal disorder, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, or a metabolic disorder.
34. The use of claim 33, wherein the disorder is a GI disorder, wherein the GI disorder is matory bowel disease.
35. The use of claim 33, wherein the disorder is cancer, diabetes, or a sterol synthesis disorder.
36. The use of claim 33, wherein the disorder is cancer.
37. The use of claim 33, wherein the disorder is a lic disorder.
38. Use of a compound or ceutically acceptable salt of any one of claims 1-28, or a pharmaceutical composition of claim 29 or 30, in the manufacture of a medicament for treating or preventing a CNS-related condition.
39. The use of claim 38, n 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 disorder, a sleep disorder, a nce-related disorder, a personality disorder, an autism spectrum disorder, a neurodevelopmental disorder, multiple sclerosis, a sterol synthesis disorder, pain, an encephalopathy secondary to a medical condition, a seizure disorder, stroke, traumatic brain injury, a movement disorder, vision impairment, hearing loss, and tinnitus.
40. The use of claim 39, wherein the CNS-related condition is a sterol synthesis er.
41. The use of claim 39, wherein the CNS-related ion is a psychotic disorder, n the psychotic disorder is schizophrenia.
42. The use of claim 39, wherein the lated condition is an autism spectrum disorder.
43. The use of claim 38, wherein the CNS-related condition is Huntington’s disease or Parkinson’s disease.
44. The use of claim 38, wherein the CNS-related condition is Alzheimer’s disease.
45. The use of claim 39, wherein the CNS-related condition is an encephalopathy secondary to a medical condition, wherein the encephalopathy secondary to a l condition is anti- NMDA receptor encephalitis. Sage Therapeutics, Inc. By the Attorneys for the Applicant N & FERGUSON
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 | |
| NZ738847A NZ738847B2 (en) | 2016-07-06 | Oxysterols and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ777726A NZ777726A (en) | 2024-05-31 |
| NZ777726B2 true NZ777726B2 (en) | 2024-09-03 |
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