NZ746825B2 - Oxysterols and methods of use thereof - Google Patents
Oxysterols and methods of use thereof Download PDFInfo
- Publication number
- NZ746825B2 NZ746825B2 NZ746825A NZ74682517A NZ746825B2 NZ 746825 B2 NZ746825 B2 NZ 746825B2 NZ 746825 A NZ746825 A NZ 746825A NZ 74682517 A NZ74682517 A NZ 74682517A NZ 746825 B2 NZ746825 B2 NZ 746825B2
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- NZ
- New Zealand
- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- disorder
- formula
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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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
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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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- 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
-
- 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
- A61P3/06—Antihyperlipidemics
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
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- 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
Abstract
Compounds are provided according to Formula (I), and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein A, R1, and R5are 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 (I-B): (I-B) or a pharmaceutically acceptable salt thereof, wherein: R1 is hydrogen or C1-6 alkyl; R5 is absent or hydrogen; Z is –C(RA)2–, –NRB–, –O–, or –S– ; X is halogen, C1-6 alkyl, or –ORC; RA is hydrogen, halogen, or C1-6 alkyl; RB is hydrogen, C1-6 alkyl, –C(O)RC, –C(O)ORC, –C(O)N(RD)2, or –S(O)2RC; RC is hydrogen or C1-6 alkyl; each RD is independently hydrogen, C1-6 alkyl, aryl, or aryl; m is an integer selected from 1, 2, and 3; n is an integer selected from 1, 2, and 3; p is an integer selected from 0, 1, 2, 3, 4, and 5; and represents a single or double bond, wherein when one is a double bond, then the other is a single bond and R5 is absent; wherein each C1-6 alkyl is ndently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, -CN, -NO2, - OH, -C1-6 , and -NH2; and wherein said aryl and heteroaryl is independently optionally tuted 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 f, wherein the compound is of Formula , Formula (II-B), or Formula (II-C): (II-A), (II-B), or (II-C).
3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein p is an r selected from 0, 1, or 2.
4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein p is 0.
5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n p is 1.
6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein p is 1 and X is halogen.
7. The compound of claim 2, or a ceutically acceptable salt thereof, wherein the compound is of Formula (II-D), Formula (II-E), or Formula (II-F): (II-D), (II-E), or
8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is C1-6 alkyl.
9. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl or ethyl.
10. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1 is –CH3 or -CH2CH3.
11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n the compound is of Formula (II-G) or Formula (II-H): (II-G) or (II-H).
12. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (II-I) or Formula (II-J): (II-I) or (II-J).
13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n Z is –C(RA)2–, –O–, or –NRB–.
14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n RA is halogen.
15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is –CH2–,–CF2–, or –C(CH3)2–.
16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is –O– or –NRB–.
17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is –NH–, –NMe–, or –NAc–.
18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n Z is –CH2–.
19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, n Z is –C(CH3)2–.
20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is –CF2–.
21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 1, n is 2, and Z is –O–.
22. The compound of claim 1, or a pharmaceutically acceptable salt f, wherein m is 2 and n is 2.
23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 3 and n is 1.
24. The compound of claim 1, or a pharmaceutically able salt thereof, wherein m is 3, n is 1, and Z is –O–.
25. The nd of claim 1, or a pharmaceutically acceptable salt f, wherein m is 2, n is 2, and Z is –O– or –NRB–.
26. The compound of claim 1, wherein the compound is selected from the group consisting , , , , , , , , , , , , , , , , , , , , , , , and .
27. The compound of claim 1, wherein the compound is a pharmaceutically able salt of a compound selected from the group consisting of: , , , , , , , , , , , , , , , , , , , , , , , and .
28. A pharmaceutical composition comprising the compound according to any one of claims 1-26, and a pharmaceutically acceptable r.
29. A pharmaceutical composition comprising the pharmaceutically acceptable salt according to any one of claims 1-25 and 27, and a pharmaceutically acceptable carrier.
30. Use of the compound or pharmaceutically acceptable salt according to any one of claims 1-27, or the pharmaceutical composition according to claim 28 or 29, in the cture of a medicament for inducing sedation or anesthesia.
31. Use of the compound or pharmaceutically acceptable salt according to any one of claims 1-27, or the ceutical composition according to claim 28 or 29, in the manufacture of a medicament for treating or preventing a disorder, wherein the disorder is a gastrointestinal (GI) disorder, a structural er affecting the GI tract, an anal disorder, colon polyps, cancer, colitis, diabetes, a sterol synthesis disorder, inflammatory bowel disease, or a metabolic disorder.
32. The use according to claim 31, wherein the disorder is inflammatory bowel disease.
33. The use according to claim 31, wherein the disorder is cancer, diabetes, or a sterol synthesis disorder.
34. The use ing to claim 31, wherein the disorder is a metabolic disorder.
35. Use of the compound or ceutically acceptable salt according to any one of claims 1-27, or the pharmaceutical composition according to claim 28 or 29, in the manufacture of a medicament for ng or preventing a CNS-related condition.
36. The use according to claim 35, wherein the CNS-related condition is an adjustment disorder, an anxiety disorder, a cognitive disorder, a dissociative disorder, an eating er, a mood er, a bipolar disorder, a dysthymic disorder, suicidality, schizophrenia or another psychotic disorder, a sleep er, a substance-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 e er, stroke, traumatic brain injury, a movement disorder, vision impairment, hearing loss, or tinnitus.
37. The use according to claim 35, wherein the CNS-related condition is a sterol synthesis disorder.
38. The use according to claim 35, wherein the CNS-related condition is schizophrenia.
39. The use ing to claim 35, wherein the lated condition is an autism spectrum disorder.
40. The use according to claim 35, wherein the CNS-related condition is Alzheimer’s disease.
41. The use according to claim 35, wherein the CNS-related ion is Huntington’s disease or Parkinson’s disease.
42. The use according to claim 35, n the CNS-related condition is anti-NMDA receptor encephalitis.
43. Use of the compound or pharmaceutically acceptable salt according to any one of claims 1-27, or the pharmaceutical composition according to claim 28 or 29, in the manufacture of a medicament for treating or preventing Smith-Lemli-Opitz Syndrome (SLOS), desmosterolosis, sitosterolemia, cerebrotendinous xanthomatosis (CTX), a mevalonate kinase deficiency syndrome (MKD), a SC4MOL gene mutation (SMO Deficiency), a n-Pick e, or an autism Disorder associated with phenylketonuria. Sage Therapeutics, Inc. By the Attorneys for the Applicant SPRUSON & FERGUSON
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662317002P | 2016-04-01 | 2016-04-01 | |
| PCT/US2017/025535 WO2017173358A1 (en) | 2016-04-01 | 2017-03-31 | Oxysterols and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ746825A NZ746825A (en) | 2024-07-26 |
| NZ746825B2 true NZ746825B2 (en) | 2024-10-30 |
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