Granted Patent B2

US 9,353,122 · App. 14/181,095 · Granted May 31, 2016

Inventors: Winston Zapanta Ong (Stoneham, MA); Pawel Wojciech Nowak (Woodcliff Lake, NJ); Ben C. Askew (Marshfield, MA); Jinsoo Kim (Brighton, MA)

Assignee: Kala Pharmaceuticals, Inc.

C07D491/107C07D239/88C07D405/12C07D413/14

Abstract

Claims (125)

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is hydrogen or C 1-6 alkyl;

R 2 is heterocyclyl;

X is a bond, —O—, or —C(═O)—;

each instance of R 3 is independently selected from the group consisting of hydrogen, F, Cl, Br, I, CN, and OH;

Y is N;

Z is optionally substituted aliphatic, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted quinolyl;

m is independently 0, 1, 2, 3, or 4; and

n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

2. The compound of claim 1 , wherein the compound is of Formula (II):

or a pharmaceutically acceptable salt thereof,

wherein:

each instance of R 4 is independently hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, or CN; and

j is 0, 1, or 2.

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

or a pharmaceutically acceptable salt thereof

wherein:

each instance of R 4 is independently hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, or CN; and

j is 0, 1, or 2.

4. The compound of claim 1 , wherein the compound is of Formula (II-b):

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is of Formula (II-c):

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein the compound is of Formula (II-c1):

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound is of Formula (II-c2):

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein the compound is of Formula (II-c3):

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein the compound is of Formula (II-c4):

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein the compound is of Formula (III):

or a pharmaceutically acceptable salt thereof,

wherein:

each instance of R 5 is independently hydrogen, optionally substituted C 1-6 alkyl, F, Cl, Br, I, or CN; and

k is 0, 1, 2, 3, 4, or 5.

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

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , wherein the compound is of Formula (III-b):

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 , wherein the compound is of Formula (III-c):

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , wherein the compound is of Formula (III-c1):

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , wherein the compound is of Formula (III-c2):

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , wherein the compound is of Formula (III-c3):

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 , wherein the compound is of Formula (III-c4):

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1 , wherein the compound is of Formula (IV):

or a pharmaceutically acceptable salt thereof,

wherein Z 1 is branched or unbranched, acyclic or cyclic C 1-6 alkyl.

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

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , wherein the compound is of Formula (IV-al):

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 1 , wherein the compound is of Formula (IV-a1-i):

or a pharmaceutically acceptable salt thereof.

22. The compound of claim 1 , wherein the compound is of Formula (IV-a1-ii):

or a pharmaceutically acceptable salt thereof.

23. The compound of claim 1 , wherein the compound is of Formula (IV-a1-iii):

or a pharmaceutically acceptable salt thereof.

24. The compound of claim 1 , wherein the compound is of Formula (IV-a1-iv):

or a pharmaceutically acceptable salt thereof.

25. The compound of claim 1 , wherein the compound is of Formula (IV-b):

or a pharmaceutically acceptable salt thereof.

26. The compound of claim 1 , wherein the compound is of Formula (IV-b1):

or a pharmaceutically acceptable salt thereof.

27. The compound of claim 1 , wherein the compound is of Formula (IV-1-i):

or a pharmaceutically acceptable salt thereof.

28. The compound of claim 1 , wherein the compound is of Formula (IV-b1-ii):

or a pharmaceutically acceptable salt thereof.

29. The compound of claim 1 , wherein the compound is of Formula (IV-b1-iii):

or a pharmaceutically acceptable salt thereof.

30. The compound of claim 1 , wherein the compound is of Formula (IV-b1-iv):

or a pharmaceutically acceptable salt thereof.

31. The compound of claim 1 , wherein the compound is of Formula (V):

or a pharmaceutically acceptable salt thereof,

wherein each of e and f is independently 1, 2, or 3.

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

or a pharmaceutically acceptable salt thereof.

33. The compound of claim 1 , wherein the compound is of Formula (V-a1):

or a pharmaceutically acceptable salt thereof.

34. The compound of claim 1 , wherein the compound is of Formula (V-a1-i):

or a pharmaceutically acceptable salt thereof.

35. The compound of claim 1 , wherein the compound is of Formula (V-a1-ii):

or a pharmaceutically acceptable salt thereof.

36. The compound of claim 1 , wherein the compound is of Formula (V-a1-iii):

or a pharmaceutically acceptable salt thereof.

37. The compound of claim 1 , wherein the compound is of Formula (V-a1-iv):

or a pharmaceutically acceptable salt thereof.

38. The compound of claim 1 , wherein the compound is of Formula (V-b):

or a pharmaceutically acceptable salt thereof.

39. The compound of claim 1 , wherein the compound is of Formula (V-b1):

or a pharmaceutically acceptable salt thereof.

40. The compound of claim 1 , wherein the compound is of Formula (V-b1-i):

or a pharmaceutically acceptable salt thereof.

41. The compound of claim 1 , wherein the compound is of Formula (V-b1-ii):

or a pharmaceutically acceptable salt thereof.

42. The compound of claim 1 , wherein the compound is of Formula (V-b1-iii):

or a pharmaceutically acceptable salt thereof.

43. The compound of claim 1 , wherein the compound is of Formula (V-b1-iv):

or a pharmaceutically acceptable salt thereof.

44. The compound of claim 1 , wherein R 2 is of the formula:

wherein each instance of p and q is independently 0, 1, 2, 3, or 4.

45. The compound of claim 44 , wherein R 2 is of the formula:

46. The compound of claim 1 , wherein R 2 is of the formula:

wherein each instance of p, q, s, and t is independently 0, 1, 2, 3, or 4.

47. The compound of claim 46 , wherein R 2 is of the formula:

48. The compound of claim 1 of one of the following formulae:

49. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

50. A compound of Formula (VI):

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is hydrogen or optionally substituted C 1-6 alkyl;

R 2 is heterocyclyl;

X is a bond, —O—, or —C(═O )—;

each instance of R 3 is independently selected from the group consisting of hydrogen, F, Cl, Br, I, CN, and OH;

Y is N;

Z is optionally substituted aliphatic, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted quinolyl;

m is independently 0, 1, 2, 3, or 4; and

n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

Assignments (8)

Continuity (3)