US2021347812A1PendingUtilityA1
Neuroactive steroids, compositions, and uses thereof
Est. expiryFeb 20, 2035(~8.6 yrs left)· nominal 20-yr term from priority
C07J 43/003C07J 7/007A61P 25/20C07J 7/0085A61K 31/58A61K 45/06C07J 21/008C07J 7/002C07J 13/007A61P 25/26A61P 25/00
69
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Claims
Abstract
Described herein are neuro-active steroids of the Formula (I): (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.
Claims
exact text as granted — not AI-modified1 - 66 . (canceled)
67 . A method for therapeutically treating a CNS-related disorder in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of (a) a compound of Formula (I) or a pharmaceutically acceptable salt thereof or (b) a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, wherein:
each X, Y, and Z is independently CH or N;
G is —C(R 3a )(R 3b )(OR 1 );
R 1 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
R 2 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy;
each of R 3a and R 3b is independently —H, -D, or C 1 -C 6 alkyl;
R a is cyano, halogen, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —S(O) m R b , —NR c R d , —C(O)R e , or —C(O)OR f ;
R b is C 1 -C 6 alkyl, —NR c R d , or —OR f ;
each of R c and R d is independently —H, C 1 -C 6 alkyl, —C(O)R e , or —C(O)OR f ;
R e is C 1 -C 6 alkyl or —NR g R h ;
R f is —H or C 1 -C 6 alkyl;
each of R g and R h is independently —H or C 1 -C 6 alkyl;
m is 0, 1, or 2;
n is 0, 1, 2, 3, or 4; and
the compound is not selected from a compound selected from:
and
wherein the CNS-related disorder is selected from anxiety disorder and seizure.
68 . The method of claim 67 , wherein R 1 is C 1 -C 6 alkyl.
69 . The method of claim 68 , wherein R 1 is —CH 3 , —CH 2 CH 3 , or —CH(CH 3 ) 2 .
70 . The method of claim 67 , wherein R 2 is C 1 -C 6 alkyl.
71 . The method of claim 70 , wherein R 2 is —CH 3 .
72 . The method of claim 67 , wherein each of R 3a and R 3b is independently —H or -D.
73 . The method of claim 67 , wherein each of R 3a and R 3b is independently —H.
74 . The method of claim 67 , wherein one of R 3a and R 3b is —H, -D, or C 1 -C 6 alkyl, and the other of R 3a and R 3b is —H.
75 . The method of claim 67 , wherein the compound Formula (I) is a compound of Formula (I-a):
76 . The method of claim 75 , wherein X is N, and Y and Z are CH.
77 . The method of claim 75 , wherein X and Z are N, and Y is CH.
78 . The method of claim 75 , wherein X, Y, and Z are N.
79 . The method of claim 75 , wherein R 1 is C 1 -C 6 alkyl.
80 . The method of claim 75 , wherein R 2 is C 1 -C 6 alkyl.
81 . The method of claim 75 , wherein each of R 3a and R 3b is independently —H or -D.
82 . The method of claim 75 , wherein one of R 3a and R 3b is —H, -D, or C 1 -C 6 alkyl, and the other of R 3a and R 3b is —H.
83 . The method of claim 75 , wherein one of R 3a and R 3b is -D or C 1 -C 6 alkyl, and the other of R 3a and R 3b is —H.
84 . The method of claim 75 , wherein n is 1.
85 . The method of claim 75 , wherein R a is C 1 -C 6 alkyl or C 1 -C 6 alkoxy.
86 . The method of claim 75 , wherein R a is —S(O) m R b , —NR c R d , —C(O)R e , or —C(O)OR f .
87 . The method of claim 75 , wherein R a is halogen.
88 . The method of claim 75 , wherein n is 1 or 2, and R a is cyano, halogen, nitro, or C 1 -C 6 alkoxy.
89 . The method of claim 67 , wherein the compound Formula (I) is a compound of Formula (I-b):
90 . The method of claim 67 , wherein the compound is selected from:
and a pharmaceutically acceptable salt thereof.
91 . The method of claim 67 , wherein the CNS-related disorder is anxiety disorder.
92 . The method of claim 91 , wherein the anxiety disorder is selected from generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), phobia, and post-traumatic stress disorder (PTSD).
93 . The method of claim 67 , wherein the CNS-related disorder is seizure.
94 . A method for positively modulating a GABAA receptor in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, wherein:
each X, Y, and Z is independently CH or N;
G is —C(R 3a )(R 3b )(OR 1 );
R 1 is C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
R 2 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy;
each of R 3a and R 3b is independently —H, -D, or C 1 -C 6 alkyl;
R a is cyano, halogen, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —S(O) m R b , —NR c R d , —C(O)R e , or —C(O)OR f ;
R b is C 1 -C 6 alkyl, —NR c R d , or —OR f ;
each of R c and R d is independently —H, C 1 -C 6 alkyl, —C(O)R e , or —C(O)OR f ;
R e is C 1 -C 6 alkyl or —NR g R h ;
R f is H or C 1 -C 6 alkyl;
each of R g and R h is independently —H or C 1 -C 6 alkyl;
m is 0, 1, or 2;
n is 0, 1, 2, 3, or 4; and
the compound is not selected from a compound selected from:
and
wherein the subject has a CNS-related disorder selected from anxiety disorder and seizure.
95 . The method of claim 94 , wherein the pharmaceutical composition is administered orally, subcutaneously, intravenously, or intramuscularly.
96 . The method of claim 94 , wherein the pharmaceutical composition is administered chronically.
97 . The method of claim 94 , wherein the CNS-related disorder is anxiety disorder.
98 . The method of claim 97 , wherein the anxiety disorder is selected from generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), phobia, and post-traumatic stress disorder (PTSD).
99 . The method of claim 94 , wherein the CNS-related disorder is seizure.
100 . The method of claim 95 , wherein the pharmaceutical composition is administered orally.
101 . The method of claim 95 , wherein the pharmaceutical composition is administered intravenously.Join the waitlist — get patent alerts
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