Inhibitors of APOL1 and methods of using same

1. Form A of Compound 2:

2. Form A of Compound 2 according to claim 1 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 1 .

3. Form A of Compound 2 according to claim 1 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 9.5±0.2, 13.2±0.2, 14.4±0.2, 19.2±0.2, 19.5±0.2, 19.8±0.2, 26.3±0.2, 26.7±0.2, and 28.6±0.2.

4. Form A of Compound 2 according to claim 1 , characterized by a 13 C NMR spectrum having a signal at at least three ppm values chosen from 178.7±0.2 ppm, 154.4±0.2 ppm, 127.8±0.2 ppm, 125.2±0.2 ppm, 102.0±0.2 ppm, 59.3±0.2 ppm, 38.9±0.2 ppm, and 24.4±0.2 ppm.

5. Form A of Compound 2 according to claim 1 , characterized by a 19 F NMR spectrum having a signal at at least one ppm value chosen from −116.0±0.2 ppm, −119.7±0.2 ppm, and −138.1±0.2 ppm.

6. A composition comprising Form A of Compound 2 according to claim 1 .

7. Hydrate Form A of Compound 2:

8. Hydrate Form A of Compound 2 according to claim 7 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 7 .

9. Hydrate Form A of Compound 2 according to claim 7 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 12.2±0.2, 19.0±0.2, 19.1±0.2, 19.6±0.2, 20.2±0.2, 22.7±0.2, 24.2±0.2, 25.4±0.2, and 25.5±0.2.

10. Hydrate Form A of Compound 2 according to claim 7 , characterized by a 13 C NMR spectrum having a signal at at least three ppm values chosen from 177.5±0.2 ppm, 157.7±0.2 ppm, 128.9±0.2 ppm, 95.4±0.2 ppm, 36.9±0.2 ppm, 23.0±0.2 ppm, and 22.3±0.2 ppm.

11. Hydrate Form A of Compound 2 according to claim 7 , characterized by a 19 F NMR spectrum having a signal at at least one ppm value chosen from −113.8±0.2 ppm, −125.8±0.2 ppm, and −132.8±0.2 ppm.

12. A composition comprising Hydrate Form A according to claim 7 .

13. Hydrate Form B of Compound 2:

14. Hydrate Form B of Compound 2 according to claim 13 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 12 .

15. Hydrate Form B of Compound 2 according to claim 13 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 3.8±0.2, 9.0±0.2, 9.3±0.2, 18.7±0.2, 19.1±0.2, 20.8±0.2, 21.1±0.2, 24.6±0.2, and 26.8±0.2.

16. Hydrate Form B of Compound 2 according to claim 13 , characterized by a 19 F NMR spectrum having a signal at at least one ppm value chosen from −117.0±0.2 ppm, −119.1±0.2 ppm, and −137.7±0.2 ppm.

17. A composition comprising Hydrate Form B of Compound 2 according to claim 13 .

18. Hydrate Form C of Compound 2:

19. Hydrate Form C of Compound 2 according to claim 18 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 14 .

20. Hydrate Form C of Compound 2 according to claim 18 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 3.7±0.2, 10.4±0.2, 10.7±0.2, 13.2±0.2, 14.6±0.2, 15.7±0.2, 18.3±0.2, 21.8±0.2, and 24.9±0.2.

21. A composition comprising Hydrate Form C of Compound 2 according to claim 18 .

22. Hydrate Form C of Compound 2 according to claim 18 , characterized by a 13 C NMR spectrum having a signal at at least three ppm values chosen from 178.2±0.2 ppm, 127.2±0.2 ppm, 116.9±0.2 ppm, 71.6±0.2 ppm, 57.6±0.2 ppm, 49.6±0.2 ppm, 35.5±0.2 ppm, and 20.0±0.2 ppm.

23. Hydrate Form C of Compound 2 according to claim 18 , characterized by a 19 F NMR spectrum having a signal at at least one ppm value chosen from −109.9±0.2 ppm, −111.5±0.2 ppm, −113.0±0.2, −120.9±0.2, −121.8±0.2 and −123.4±0.2 ppm.

24. Hydrate Form D of Compound 2:

25. Hydrate Form D of Compound 2 according to claim 24 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 19 .

26. Hydrate Form D of Compound 2 according to claim 24 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 4.1±0.2, 5.0±0.2, 7.7±0.2, 8.2±0.2, and 15.2±0.2.

27. A composition comprising Hydrate Form D of Compound 2 according to claim 24 .

28. Hydrate Form E of Compound 2:

29. Hydrate Form E of Compound 2 according to claim 28 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 22 .

30. Hydrate Form E of Compound 2 according to claim 28 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 6.5±0.2, 7.7±0.2, 11.4±0.2, 14.3±0.2, and 18.9±0.2.

31. A composition comprising Hydrate Form E of Compound 2 according to claim 28 .

32. Hydrate Form F of Compound 2:

33. Hydrate Form F of Compound 2 according to claim 32 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 25 .

34. Hydrate Form F of Compound 2 according to claim 32 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 3.8±0.2, 7.6±0.2, and 11.4±0.2.

35. A composition comprising Hydrate Form F of Compound 2 according to claim 32 .

36. MTBE Solvate Form of Compound 2:

37. MTBE Solvate Form of Compound 2 according to claim 36 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 28 .

38. MTBE Solvate Form of Compound 2 according to claim 36 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 6.0±0.2, 6.8±0.2, 8.4±0.2, 18.0±0.2, 19.4±0.2, and 20.2±0.2.

39. A composition comprising MTBE Solvate Form of Compound 2 according to claim 36 .

40. DMF Solvate Form of Compound 2:

41. DMF Solvate Form of Compound 2 according to claim 40 , characterized by an X-ray powder diffractogram having a signal at at least two two-theta values chosen from 5.6±0.2, 9.3±0.2, 15.3±0.2, 18.0±0.2, and 20.1±0.2.

42. DMF Solvate Form of Compound 2 according to claim 40 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 31 .

43. A composition comprising DMF Solvate Form of Compound 2 according to claim 40 .

44. Amorphous Form of Compound 2:

45. Amorphous Form of Compound 2 according to claim 44 , characterized by an X-ray powder diffractogram substantially similar to that in FIG. 34 .

46. Amorphous form of Compound 2 according to claim 44 , characterized by a 13 C NMR spectrum having a signal at at least three ppm values chosen from 174.7±0.2 ppm, 161.3±0.2 ppm, 130.2±0.2 ppm, 120.9±0.2 ppm, 74.7±0.2 ppm, and 20.5±0.2 ppm.

47. Amorphous form of Compound 2 according to claim 44 , characterized by a 19 F NMR spectrum having a signal at at least one ppm value chosen from −122.4±0.2 ppm and −131.1±0.2 ppm.

48. A method of treating focal segmental glomerulosclerosis and/or non-diabetic kidney disease comprising administering to a patient in need thereof at least one entity according to any one of claims 1, 7, 13, 18, 24, 24, 28, 36, 40, or 44 .

49. A method of inhibiting APOL1 activity comprising contacting said APOL1 with at least one entity according to any one of claims 1, 7, 13, 18, 24, 28, 32, 36, 40, or 44 .

50. At least one entity A compound chosen from compounds of Formula (I):

deuterated derivatives thereof, pharmaceutically acceptable salts of those compounds and deuterated derivatives, and solvates of any of the foregoing, wherein:

(i) each R 1 is independently chosen from

halogen groups,

hydroxy,

cyano,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkyl groups,

C 2 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkenyl groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic hydroxyalkyl groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkoxy groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkyl groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkoxy groups,

benzyloxy groups,

3 to 6-membered heterocycloalkenyl groups,

3 to 6-membered heterocycloalkyl groups, and

5 and 6-membered heteroaryl groups;

(ii) each R 2 is independently chosen from

halogen groups,

cyano,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkoxy groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkoxy groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkyl groups, and

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkyl groups;

(iii) m is chosen from 0 to, 1, 2, 3, and 4;

(iv) n is chosen from 0 to, 1, 2, 3, 4, and 5;

(v) Y is chosen from divalent C 1 -C 8 linear, C 3 -C 8 branched, and C 3 -C 8 cyclic alkyl groups, wherein the divalent alkyl group is optionally substituted with at least one group chosen from

C 1 -C 4 alkyl groups,

halogen groups, and

hydroxy;

(vi) each of R 3 and R 4 is independently chosen from

hydrogen,

C 1 -C 3 linear, C 3 branched, and C 3 cyclic alkyl groups,

C 1 -C 3 linear, C 3 branched, and C 3 cyclic hydroxyalkyl groups, and

C 1 -C 3 linear, C 3 branched, and C 3 cyclic haloalkyl groups, or

each R 3 and R 4 , together with the carbon atom to which they are attached, form a C 3 -C 6 cycloalkyl group or carbonyl group;

(vii) each of R 5 and R 6 is independently chosen from

hydrogen,

hydroxy,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkyl groups,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkyl groups, and

—OC(O)C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkyl groups; and

(viii) each of R 7 , R 8 , and R 9 is independently chosen from

hydrogen,

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic alkyl groups, and

C 1 -C 4 linear, C 3 -C 4 branched, and C 3 -C 4 cyclic haloalkyl groups.

51. The compound, deuterated derivative, pharmaceutically acceptable salt, or solvate according to claim 50 , chosen from Compound 2:

deuterated derivatives thereof, pharmaceutically acceptable salts thereof, and solvates of any of the foregoing.

52. The compound, deuterated derivative, pharmaceutically acceptable salt, or solvate according to claim 50 , chosen from Compound 87:

deuterated derivatives thereof, pharmaceutically acceptable salts thereof, and solvates of any of the foregoing.

53. A pharmaceutical composition comprising the compound, deuterated derivative, pharmaceutically acceptable salt, or solvate according to claim 51 or 52 , and a pharmaceutically acceptable carrier.