Neuroactive steroids, compositions, and uses thereof

1. A compound of the Formula (Ib):

or a pharmaceutically acceptable salt thereof,

wherein:

A is an optionally substituted nitrogen-containing bicyclic heteroaryl or bicyclic heterocyclyl;

L is —C(R 3 )(R 3 )—, —O—, —S—, or —NR 3 —;

R 1 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, or heterocyclyl;

R 2 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy;

each R 3 is independently hydrogen;

R 5 is absent or hydrogen; and

is 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 or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (Ib) is a compound of Formula (Ib-3) or (Ib-4):

or a pharmaceutically acceptable salt thereof,

wherein:

R 4 is cyano, nitro, hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R b )(R c ), —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b )(R c );

each R a is independently hydrogen or C 1 -C 6 alkyl;

each R b and R c is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or

R b and R c , together with the nitrogen atom to which they are bound to form a ring; and

n is 0, 1, 2, or 3.

3. The compound or pharmaceutically acceptable salt of claim 2 , wherein n is 0.

4. The compound or pharmaceutically acceptable salt of claim 2 , wherein n is 1 or 2, and wherein each R 4 is independently cyano, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , or —S(O) 0-2 R a .

5. The compound or pharmaceutically acceptable salt of claim 4 , wherein each R a is independently C 1 -C 6 alkyl.

6. The compound or pharmaceutically acceptable salt of claim 5 , wherein each R a is methyl.

7. The compound or pharmaceutically acceptable salt of claim 4 , wherein each R 4 is —S(O) 2 R a .

8. The compound or pharmaceutically acceptable salt of claim 7 , wherein R a is methyl.

9. The compound or pharmaceutically acceptable salt of claim 2 , wherein R 1 is C 1 -C 6 alkyl and R 4 is —C(O)R a .

10. The compound or pharmaceutically acceptable salt of claim 2 , wherein n is 0 or 1, R 1 is hydrogen or C 1 -C 6 alkyl; and R 2 is methyl.

11. The compound or pharmaceutically acceptable salt of claim 2 , wherein each R 4 is independently C 1 -C 6 alkyl, —C(O)R a , or —S(O) 0-2 R a .

12. The compound of pharmaceutically acceptable salt of claim 1 , wherein A is benzotriazole, azabenzotriazole, diazabenzotriazole, benzopyrazole, azabenzopyrazole, or diazabenzopyrazole.

13. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, or heterocyclyl.

14. The compound or pharmaceutically acceptable salt of claim 12 , wherein R 1 is methyl, ethyl, or isopropyl.

15. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 2 is methyl.

16. A compound selected from

or a pharmaceutically acceptable salt thereof.

17. A compound of Formula (Ia):

or a pharmaceutically acceptable salt thereof;

wherein:

Ring A is an optionally substituted 5-membered or 6-membered monocyclic heterocyclyl or an optionally substituted 5-membered or 6-membered monocyclic heteroaryl, wherein the heterocyclyl or heteroaryl of ring A comprises 1, 2, 3, or 4 nitrogen atoms and wherein the heterocyclyl or heteroaryl of ring A is linked through a nitrogen atom;

L is —C(R 3 )(R 3 )—, —O—, —S—, or —NR 3 —;

R 1 is unsubstituted C 1 -C 6 alkyl;

each R 3 is hydrogen;

R 5 is absent or hydrogen; and

is 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.

18. The compound or pharmaceutically acceptable salt of claim 17 , wherein each is a single bond and R 5 is hydrogen.

19. The compound or pharmaceutically acceptable salt of claim 18 , wherein R 1 is methyl, ethyl, or isopropyl, each of which is unsubstituted.

20. The compound or pharmaceutically acceptable salt of claim 19 , wherein R 1 is unsubstituted methyl or unsubstituted ethyl.

21. The compound or pharmaceutically acceptable salt of claim 17 , wherein the compound of Formula (Ia) is a compound of Formula (Ia-1) or a compound of Formula (Ia-2):

or a pharmaceutically acceptable salt thereof.

22. The compound or pharmaceutically acceptable salt of claim 17 , wherein ring A is an optionally substituted 5-membered or 6-membered monocyclic heteroaryl, wherein the heteroaryl of ring A comprises 2, 3, or 4 nitrogen atoms and wherein the heteroaryl of ring A is linked through a nitrogen atom.

23. The compound or pharmaceutically acceptable salt of claim 17 , wherein the compound of Formula (Ia) is a compound of Formula (Ia-3) or a compound of Formula (Ia-4):

or a pharmaceutically acceptable salt thereof,

wherein

R 4 is cyano, nitro, hydroxy, halo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —C(O)R a , —C(O)N(R b )(R c ), —C(O)OR a , —N(R b )(R c ), —OC(O)N(R b )(R c ), —OC(O)OR a , —OC(O)R a , —S(O) 0-2 R a , —S(O) 0-2 OR a , or —S(O) 0-2 N(R b )(R c );

each R a is independently hydrogen or C 1-6 alkyl;

each R b and R c is independently hydrogen, C 1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or

R b and R c , together with the nitrogen atom to which they are bound to form a ring; and

n is 0, 1, 2, or 3.

24. The compound or pharmaceutically acceptable salt of claim 23 , wherein n is 0, and ring A is

25. The compound or pharmaceutically acceptable salt of claim 24 , wherein n is 0, and ring A is

26. The compound or pharmaceutically acceptable salt of claim 23 , wherein n is 1 or 2, and each R 4 is independently cyano, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R a , or —S(O) 0-2 R a .

27. The compound or pharmaceutically acceptable salt of claim 26 , wherein n is 1, and R 4 is —C(O)CH 3 , —S(O) 2 CH 3 , cyano, halo, or C 1-6 alkyl.

28. A compound selected from

or a pharmaceutically acceptable salt thereof.

29. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

30. A method of (a) therapeutically treating depression, insomnia, seizure, epilepsy, tremor or generalized anxiety disorder or (b) inducing sedation or anesthesia in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt according to claim 1 .

31. The method of claim 30 , wherein the depression is postnatal depression.

32. The method of claim 30 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally.

33. The method of claim 30 , wherein the compound or pharmaceutically acceptable salt thereof is administered intramuscularly.