Inhibitors of complement factors and uses thereof

1. A compound represented by formula I or II:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is hydrogen, halogen, amino, hydroxyl, alkoxy, or alkylthio;

W is N;

V and X are selected such that either V is CR a and X is N, or V is N and X is CR b ;

R a is hydrogen, halogen, nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, or alkyl;

R b is hydrogen, halogen, nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;

each U independently is N or CR c ;

each R c independently is hydrogen, halogen, alkyl, or alkoxy;

ring Z 1 is a five- or six-membered aryl or heteroaryl;

ring Z 2 is a five- or six-membered heterocycle;

each R 2 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, alkoxy, alkylthio, acyl, amidino, azido, carbamoyl, carboxyl, carboxyester, guanidine, haloalkyl, haloalkoxy, heteroalkyl, imino, oxime, phosphonate, dialkylphosphine oxide, sulfonyl, sulfonamido, sulfonyl urea, sulfinyl, sulfinic acid, sulfonic acid, thiocyanate, thiocarbonyl, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; or two vicinal R 2 , together with the intervening carbon atoms to which they attach, combine to form a 5- or 6-membered carbocycle, 5- or 6-membered heterocycle, 5- or 6-membered aryl, or 5- or 6-membered heteroaryl;

n is 0 or an integer selected from 1-4, as valency permits;

each R 6 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, oxo, carboxyl, alkoxy, alkylthio, acyl, amidino, azido, carbamoyl, carboxyl, carboxyester, guanidine, haloalkyl, haloalkoxy, heteroalkyl, imino, oxime, phosphonate, dialkylphosphine oxide, sulfonyl, sulfonamido, sulfonyl urea, sulfinyl, sulfinic acid, sulfonic acid, thiocyanate, thiocarbonyl, alkyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; or any two R 6 , together with the intervening carbon atom(s) to which they attach, combine to form a carbocycle or heterocycle;

q is 0 or an integer selected from 1-4, as valency permits;

R 3 is

M is N(R 8 ) 3 , N(R 8 ) 2 , OR 8 or SR 8 ;

each R 8 is independently hydrogen, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; and

R 3a and R 3b independently are hydrogen, alkyl, acyl, alkenyl, alkynyl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; or R 3a and R 3b , together with the boron atom and the two intervening oxygen atoms that separate them, combine to form a monocyclic or polycyclic heterocyclyl; or R 3a , R 3b , and M, together with the boron atom and the intervening oxygen atoms, combine to form a polycyclic heterocycle.

2. The compound of claim 1 , wherein the compound is represented by formula I-a or II-a:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein R 1 is hydroxyl, C 1-3 alkoxy, or amino.

4. The compound of claim 1 , wherein each R 2 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, alkoxy, alkylthio, phosphonate, dialkylphosphine oxide, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; or two vicinal R 2 , together with the intervening carbon atoms to which they attach, combine to form a 5- or 6-membered carbocycle, 5- or 6-membered heterocycle, 5- or 6-membered aryl, or 5- or 6-membered heteroaryl.

5. The compound of claim 1 , wherein each R 2 is independently substituted with deuterium.

6. The compound of claim 1 , wherein each R a independently is hydrogen, halogen, amino, hydroxyl, alkoxy or alkyl.

7. The compound of claim 1 , wherein R b is hydrogen, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl.

8. The compound of claim 1 , wherein each R c independently is hydrogen, halogen, or alkyl.

9. The compound of claim 1 , wherein U is CR c .

10. The compound claim 1 , wherein ring Z 1 is phenyl or a five- or six-membered heteroaryl.

11. The compound of claim 10 , wherein ring Z 1 is phenyl.

12. The compound of claim 11 , wherein the compound is represented by formula I-b or II-b:

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 12 , wherein the compound is a compound represented by formula I-c or II-c:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 12 , wherein the compound is represented by formula I-c-1 or I-c-2:

or a pharmaceutically acceptable salt thereof,

wherein R 2a is alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl.

15. The compound of claim 14 , wherein R 2a is methyl, difluoromethyl, —CF 2 CHF 2 , —CHFCF 3 , —CH 2 CF 3 , —(CH 2 CH 2 O) 2 CH 3 ,

wherein m is an integer from 2 to 6.

16. The compound of claim 14 , wherein R 3 is

17. The compound of claim 16 , wherein R 3a and R 3b are hydrogen.

18. The compound of claim 16 , wherein R 3a and R 3b , together with the boron atom and the two intervening oxygen atoms that separate them, combine such that R 3 is a heterocyclyl.

19. The compound of claim 18 , wherein R 3 is

wherein:

each R 5 independently is halogen, nitro, cyano, amino, acylamino, amido, hydroxyl, oxo, carboxy, alkoxy, alkylthio, alkyl, aralkyl, heteroaralkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; or any two R 5 , independently, together with the intervening carbon atom(s) to which they attach, combine to form a carbocycle or heterocycle; and

p is 0 or an integer selected from 1-6, as valency permits.

20. The compound of claim 19 , wherein R 3 is

21. The compound of claim 20 , wherein R 3 is

22. The compound of claim 14 , wherein R 3 is

and

R 3a , R 3b , and M, together with the boron atom and the intervening atoms, combine such that R 3 is a polycyclic heterocycle.

23. The compound of claim 22 , wherein R 3 is

wherein R d is H or C 1 -C 4 alkyl.

24. The compound of claim 12 , wherein the compound is represented by formula II-b-1, II-b-2, or II-b-3:

or a pharmaceutically acceptable salt thereof.

25. The compound of claim 24 , wherein ring Z 2 is

26. The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

27. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

28. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

29. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

30. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

31. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

32. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

33. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

34. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

35. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

36. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

37. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

38. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

39. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

40. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

41. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

42. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

43. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

44. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

45. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

46. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

47. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

48. The compound according to claim 26 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.