COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

1 . A compound of the Formula (I):

or a pharmaceutically acceptable salt thereof;

wherein:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-5 haloalkyl (e.g., C 1-3 haloalkyl), C 1-5 alkyl (e.g., C 1-3 alkyl), C 2-6 alkenyl, or C 3-6 carbocylyl;

each of R 2a and R 2b is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; or R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 5 is absent or hydrogen;

each of R 7a and R 7b is independently hydrogen or halogen;

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 5 is absent.

2 . The compound of claim 1 , wherein the compound is a compound of Formula (I-a):

or a pharmaceutically acceptable salt thereof;

wherein:

R 6 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, C 1-6 haloalkyl, halogen, cyano, nitro, OR A6 , C(═O)R A6 , C(═O)OR A6 , SR B6 , S(═O)R B6 , S(═O) 2 R B6 , N(R C6 )(R D6 ) C(═O)N(R C6 )(R D6 ), N(R C6 )C(═O)R A6 ; and

n is 0, 1, 2, or 3;

wherein R A6 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or C 1-6 haloalkyl; R B6 is C 1-6 alkyl or C 3-6 carbocylyl; and each of R C6 and R D6 is independently hydrogen, C 1-6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, or R C6 and R D6 together with the nitrogen atom to which they are attached form a ring (e.g., a 3-6-membered ring (e.g., carbocycyl or heterocyclyl ring)).

3 . The compound of any one of the preceding claims , wherein A is a carbon bound (e.g., A linked through a carbon atom) 5 or 6-membered heteroaryl, or 6-membered aryl.

4 . The compound of claim 3 , wherein A is:

wherein:

X is —O—, —S—, or —N(R N )—, wherein R N is independently hydrogen, C 1-6 alkyl, —C(═O)R GA , —C(═O)OR GA , —C(═O)N(R GA ) 2 , —S(═O) 2 R GA , —S(═O) 2 OR GA , —S(═O) 2 N(R GA ) 2 , or a nitrogen protecting group;

each instance of R 6a , R 6b , R 6c , R 6d , and R 6e is, independently, hydrogen, halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —S(═O) 2 R GA , —S(═O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or 3- to 6-membered heterocyclyl; or two of R 6a , R 6b , R 6c , R 6d , and R 6e are taken with the atoms to which they are attached to form a heterocyclyl, aryl, or heteroaryl ring; and

each instance of R GA is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, 3- to 6-membered heterocyclyl, aryl, heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R GA groups are taken with the intervening atoms to form a heterocyclyl or heteroaryl ring.

5 . The compound of claim 4 , wherein at least one of R 6a , R 6b , R 6c , R 6d , and R 6e is hydrogen.

6 . The compound of claim 4 , wherein at least one of R 6a , R 6b , R 6c , R 6d , and R 6e is C 1-2 alkyl, —CO 2 R GA , —C(═O)R GA , —CN, —NO 2 , or halogen, wherein R GA is C 1-2 alkyl.

7 . The compound of claim 5 , wherein at least one of R 6a , R 6b , R 6c , R 6d , and R 6e is —CH 3 .

8 . The compound of claim 4 , wherein R 6a , R 6b , R 6c , R 6d , and R 6e are hydrogen.

9 . The compound of claim 4 , wherein A is a ring comprising at least one nitrogen atom.

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

wherein:

Ring E is heterocyclyl or heteroaryl.

11 . The compound of claim 10 , wherein E is a ring comprising at least one nitrogen atom.

12 . The compound of claim 11 , wherein E is selected from:

13 . The compound of any one of the preceding claims , wherein A is:

14 . The compound of any one of claims 10-12 , wherein E is a ring comprising at least two nitrogen atoms.

15 . The compound of claim 14 , wherein E is a ring comprising at least two nitrogen atoms and at least one of R 2 , R 3a , R 4a or R 4b is not hydrogen.

16 . The compound of any one of claims 10-15 , wherein E is a ring comprising at least three nitrogen atoms.

17 . The compound of any one of claims 10-16 , wherein E is a ring comprising four nitrogen atoms.

18 . The compound of claim 17 , wherein at least one of R 2 , R 3a , R 4a or R 4b is not hydrogen.

19 . The compound of any one of claims 10-18 , wherein E is a ring comprising 2, 3 or 4 nitrogen atoms.

20 . The compound of any one of claims 10-19 , wherein E is a ring selected from pyrazole, triazole, tetrazole, indazole, benzotriazole, triazolopyridine, triazolopyrazine, pyrazolopyrazine, or morpholine.

21 . The compound of any one of claims 1-2 , wherein A is a 6-membered heterocyclyl ring (e.g., a 6-membered heterocyclyl ring comprising at least two heteroatoms).

22 . The compound of any one of claims 1-2 , wherein A is a 5-6-membered heterocyclyl ring, and n is 1 or 2.

23 . The compound of claim 10 , wherein E is morpholine and n is 1 or 2.

24 . The compound of any one of the preceding claims , wherein A is an aryl ring.

25 . The compound of any one of the preceding claims , wherein A is phenyl and n is 1 or 2.

26 . The compound of any one of the preceding claims , wherein R 1 is hydrogen, substituted C 1-3 alkyl, or unsubstituted C 1-3 alkyl.

27 . The compound of any one of the preceding claims , wherein R 1 is hydrogen, methyl, or methoxymethyl.

28 . The compound of claim 27 , wherein R 1 is methyl.

29 . The compound of any one of the preceding claims , wherein R 2 is hydrogen, —OR A2 , wherein R A2 is hydrogen, or substituted or unsubstituted C 1-6 alkyl (e.g., methyl, ethyl).

30 . The compound of any one of the preceding claims , wherein R 3a is —OR A3 , wherein R A3 is hydrogen, or substituted or unsubstituted C 1-6 alkyl (e.g., methyl).

31 . The compound of claim 1 , wherein R 3a and R 3a are joined to form an oxo (═O) group.

32 . The compound of any one of the preceding claims , wherein R 4a is hydrogen, substituted C 1-6 alkyl, or unsubstituted C 1-6 alkyl (e.g., methyl).

33 . The compound of any one of the preceding claims , wherein R 4b is hydrogen, or substituted C 1-6 alkyl, or unsubstituted C 1-6 alkyl (e.g., methyl).

34 . The compound of claim 1 , wherein R 4a is hydrogen, and R 4b is substituted C 1-6 alkyl or unsubstituted C 1-6 alkyl (e.g., methyl).

35 . The compound of any one of the preceding claims , wherein each of R 4a and R 4a is independently unsubstituted C 1-6 alkyl (e.g., methyl).

36 . The compound of any one of the preceding claims , wherein each of R 4a and R 4a is independently hydrogen.

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

38 . The compound of any one of the preceding claims , wherein n is 0.

39 . The compound of any one of the preceding claims , wherein n is 1 and R 6 is substituted or unsubstituted C 1-6 alkyl, C 1-6 haloalkyl, halogen (e.g., —F, —Br, —Cl), 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 substituted or unsubstituted C 1-6 alkyl (e.g., methyl, ethyl), C 1-6 haloalkyl (e.g., —CF 3 ), and R B6 is substituted or unsubstituted C 1-6 alkyl.

40 . The compound of any one of the preceding claims , wherein n is 1 and R 6 is halogen (e.g., —F, —Br, —Cl) or cyano.

41 . The compound of any one of the preceding claims , wherein n is 1 and R 6 is substituted or unsubstituted C 1-6 alkyl (e.g., methyl).

42 . The compound of any one of the preceding claims , wherein n is 1 and R 6 is C 1-6 haloalkyl, —OR A6 , or —C(═O)OR A6 , wherein R A6 is hydrogen or substituted or unsubstituted C 1-6 alkyl (e.g., methyl, ethyl), C 1-6 haloalkyl (e.g., —CF 3 ).

43 . The compound of any one of the preceding claims , wherein n is 1 and R 6 is SR B6 , —S(═O)R B6 , or S(═O) 2 R B6 , wherein R B6 is substituted or unsubstituted C 1-6 alkyl (e.g., methyl).

44 . The compound of any one of the preceding claims , wherein n is 2 and R 6 is independently selected from substituted or unsubstituted C 1-6 alkyl, C 1-6 haloalkyl, halogen (e.g., —F, —Br, —Cl), 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 substituted or unsubstituted C 1 -6 alkyl (e.g., methyl, ethyl), C 1-6 haloalkyl (e.g., —CF 3 ), and R B6 is substituted or unsubstituted C 1-6 alkyl.

45 . The compound of any one of the preceding claims , wherein n is 2 and R 6 is independently selected from halogen (e.g., —F, —Br, —Cl).

46 . The compound of any one of the preceding claims , wherein n is 2 and one of R 6 is fluorine.

47 . The compound of any one of the preceding claims , wherein R 1 is unsubstituted C 1-3 alkyl and at least one of R 2 , R 3a , R 4a or R 4b is not hydrogen.

48 . The compound of claim 10 , wherein the compound is of the Formula (II-b) and E is a heteroaryl ring comprising at least 3 nitrogen atoms.

49 . The compound of claim 1 , wherein the compound is:

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

51 . 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:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 3-6 carbocylyl;

R 2 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 7a is hydrogen or halogen;

R 7b is hydrogen;

R 5 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 5 is absent.

52 . A method of administering an effective amount of a compound, a pharmaceutically acceptable salt thereof, or pharmaceutical composition of a compound of claim 1 , to a subject in need thereof, wherein the subject experiences sedation and/or anesthesia within two hours of administration.

53 . The method of claim 52 , wherein the subject experiences sedation and/or anesthesia within one hour of administration.

54 . The method of claim 52 , wherein the subject experiences sedation and/or anesthesia instantaneously.

55 . The method of claim 52 , wherein the compound is administered by intravenous administration.

56 . The method of claim 52 , wherein the compound is administered chronically.

57 . The method of claim 52 , wherein the subject is a mammal.

58 . The method of claim 57 , wherein the subject is a human.

59 . The method of claim 52 , wherein the compound is administered in combination with another therapeutic agent.

60 . 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:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 3-6 carbocylyl;

R 2 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 7a is hydrogen or halogen;

R 7b is hydrogen;

R 5 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 5 is absent.

61 . 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:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 3-6 carbocylyl;

R 2 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 7a is hydrogen or halogen;

R 7b is hydrogen;

R 5 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 5 is absent.

62 . The method of claim 61 , wherein the status epilepticus is convulsive status epilepticus (e.g., early status epilepticus, established status epilepticus, refractory status epilepticus, super-refractory status epilepticus) or non-convulsive status epilepticus, (e.g., generalized status epilepticus, complex partial status epilepticus).

63 . 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, a pharmaceutically acceptable salt thereof, or pharmaceutical composition of one of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof;

wherein:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 3-6 carbocylyl;

R 2 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 7a is hydrogen or halogen;

R 7b is hydrogen;

R 5 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 5 is absent.

64 . A method for treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any of the preceding claims , or a pharmaceutically acceptable salt thereof.

65 . The method of claim 64 , 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.

66 . The method of claim 64 , wherein the compound is administered orally.

67 . The method of claim 64 , wherein the compound is administered intramuscularly.

68 . The method of claim 64 , wherein the subject is a subject with Rett syndrome, Fragile X syndrome, or Angelman syndrome.

69 . The method of claim 64 , 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.

70 . The method of claim 64 , wherein the CNS-related disorder is depression (e.g., post-partum depression).

71 . The method of claim 64 , wherein the CNS-related disorder is tremor (e.g., essential tremor).

72 . The method of claim 64 , wherein the CNS-related disorder is an eating disorder (e.g., anorexia nervosa, bulimia nervosa, binge-eating disorder, cachexia).

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

or a pharmaceutically acceptable salt thereof;

wherein:

Ring A is carbocyclyl, heterocyclyl, aryl, or heteroaryl;

R 1 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 3-6 carbocylyl;

R 2 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocylyl, or —OR A2 , wherein R A2 is hydrogen or C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl;

R 3a is hydrogen or —OR A3 , wherein R A3 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 3b is hydrogen; or R 3a and R 3b are joined to form an oxo (═O) group;

R 4a is hydrogen, C 1-6 alkyl, or —OR A4 , wherein R A4 is hydrogen, C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, C 2-6 alkynyl, or C 3-6 carbocylyl, and R 4b is hydrogen or C 1-6 alkyl; R 4a and R 4b are joined to form an oxo (═O) group; or R 4a and R 4b 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 7a is hydrogen or halogen;

R 7b is hydrogen;

R 5 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 5 is absent;

and a sterile diluent.