COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

1 . A compound of the Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

2 . The compound of claim 1 , wherein R 1 is substituted or unsubstituted C 1-6 alkyl (e.g., haloalkyl).

3 . The compound of any one of the preceding claims, wherein R 1 is methyl or CF 3 .

4 . The compound of any one of the preceding claims, wherein R 2a is methyl.

5 . The compound of any one of the preceding claims, wherein R 2b is hydrogen.

6 . The compound of any one of the preceding claims, wherein R 2a is methyl and R 2b is hydrogen.

7 . The compound of any one of the preceding claims, wherein represents a single bond.

8 . The compound of any one of the preceding claims, wherein the compound of Formula (I) is a compound of Formula (II) or Formula (III):

or a pharmaceutically acceptable salt thereof, wherein A, R 1 , R 2a , and R 2b are defined as for Formula (I).

9 . The compound of any one of the preceding claims, wherein the compound of Formula (II) is a compound of Formula (II-a) or Formula (II-b):

or a pharmaceutically acceptable salt thereof, wherein A and R 1 are defined as for Formula (I).

10 . The compound of any one of the preceding claims, wherein the compound of Formula (III) is a compound of Formula (III-a) or Formula (III-b):

or a pharmaceutically acceptable salt thereof, wherein A and R 1 are defined as for Formula (I).

11 . The compound of any one of the preceding claims, wherein A is heterocyclyl or heteroaryl (e.g., nitrogen-containing heterocyclyl or a nitrogen-containing heteroaryl).

12 . The compound of any one of the preceding claims, wherein A is monocyclic or bicyclic.

13 . The compound of any one of the preceding claims, wherein A is substituted with at least one R A , wherein R A is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, C 1-6 haloalkyl, halogen, cyano, —OR A6 , —C(═O)OR A6 , —SR B6 , —S(═O)R B6 , or S(═O) 2 R B6 , wherein R A6 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, or C 1-6 haloalkyl, and R B6 is C 1-6 alkyl or C 3-6 carbocyclyl.

14 . The compound of claim 13 , wherein R A is C 1-6 alkyl, halogen, or cyano.

15 . The compound of any one of claims 13 - 14 , wherein A is substituted with 1-3 instances of R A .

16 . A compound of the Formula (IV):

or a pharmaceutically acceptable salt thereof wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen;

R A is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, C 1-6 haloalkyl, halogen, cyano, —OR A6 , —C(═O)OR A6 , —SR B6 , —S(═O)R B6 , or S(═O) 2 R B6 , wherein R A6 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, or C 1-6 haloalkyl, and R B6 is C 1-6 alkyl or C 3-6 carbocyclyl;

n is 0, 1, 2 or 3; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

17 . The compound of claim 16 , wherein R 1 is substituted or unsubstituted C 1-6 alkyl (e.g., haloalkyl).

18 . The compound of any one of claims 16 - 17 , wherein R 1 is methyl or CF 3 .

19 . The compound of any one of claims 16 - 18 , wherein R 2a is methyl.

20 . The compound of any one of claims 16 - 19 , wherein R 2b is hydrogen.

21 . The compound of any one of claims 16 - 20 , wherein R 2a is methyl and R 2b is hydrogen.

22 . The compound of any one of claims 16 - 21 , wherein represents a single bond.

23 . The compound of claims 16 - 22 , wherein the compound of Formula (IV) is a compound of Formula (V) or Formula (VI):

or a pharmaceutically acceptable salt thereof, wherein A, R 1 , R 2a , R 2b , R A , and n are defined as for Formula (IV).

24 . The compound of any one of claims 16 - 23 , wherein the compound of Formula (V) is a compound of Formula (V-a) or Formula (V-b):

or a pharmaceutically acceptable salt thereof, wherein A, R 1 , R 2 , R b , R A , and n are defined as for Formula (IV).

25 . The compound of any one of claims 16 - 24 , wherein the compound of Formula (VI) is a compound of Formula (VI-a) or Formula (VI-b):

or a pharmaceutically acceptable salt thereof, wherein A, R 1 , are defined as for Formula (I).

26 . The compound of any one of the preceding claims, wherein A is selected from:

27 . The compound of any one of the preceding claims, wherein A is selected from:

28 . The compound of any one of the preceding claims, wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

29 . A pharmaceutical composition comprising a compound of any one of the preceding claims and a pharmaceutically acceptable excipient.

30 . A method of inducing sedation and/or anesthesia in a subject, comprising administering to the subject an effective amount of a compound of the Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

31 . A method of administering an effective amount of a compound, a pharmaceutically acceptable salt thereof, or pharmaceutical composition of any one of the preceding claims to a subject in need thereof, wherein the subject experiences sedation and/or anesthesia within two hours of administration.

32 . The method of claim 31 , wherein the subject experiences sedation and/or anesthesia within one hour of administration.

33 . The method of claim 31 , wherein the subject experiences sedation and/or anesthesia instantaneously.

34 . The method of claim 31 , wherein the compound is administered by intravenous administration.

35 . The method of claim 31 wherein the compound is administered chronically.

36 . The method of claim 31 , wherein the subject is a mammal.

37 . The method of claim 36 , wherein the subject is a human.

38 . The method of claim 31 , wherein the compound is administered in combination with another therapeutic agent.

39 . A method for treating seizure in a subject, comprising administering to the subject an effective amount of a compound of the Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

40 . A method for treating epilepsy or status or status epilepticus in a subject, the method comprising administering to the subject an effective amount of a compound of the Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

41 . A method for treating disorders related to GABA function in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutical composition comprising a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

42 . A method for treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent.

43 . The method of claim 42 , wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, or tinnitus.

44 . The method of claim 42 , wherein the compound is administered orally.

45 . The method of claim 42 , wherein the compound is administered intramuscularly.

46 . The method of claim 42 , wherein the subject is a subject with Rett syndrome, Fragile X syndrome, or Angelman syndrome.

47 . The method of claim 42 , wherein the CNS-related disorder is a sleep disorder, an eating disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, or tinnitus.

48 . The method of claim 42 , wherein the CNS-related disorder is depression (e.g., post-partum depression).

49 . The method of claim 42 , wherein the CNS-related disorder is tremor (e.g., essential tremor).

50 . The method of claim 42 , wherein the CNS-related disorder is an eating disorder (e.g., anorexia nervosa, bulimia nervosa, binge-eating disorder, cachexia).

51 . A kit comprising a solid composition comprising a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A is aryl, heterocyclyl or heteroaryl;

R 1 is C 1-6 alkyl;

R 2a is C 1-6 alkyl;

R 2b is hydrogen or C 1-6 alkyl;

or R 2a and R 2b are joined to form an oxo (═O) group;

or R 2a and R 2b together with the carbon atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring));

R 3 is absent or hydrogen; and

represents a single or double bond, wherein when one of is a double bond, the other is a single bond; and when one of the is a double bond, R 3 is absent; and a sterile diluent.