Boron-containing small molecules
This invention provides, among other things, novel compounds useful for treating inflammatory conditions, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.
1. A compound having a structure according to the formula:
wherein
X is selected from the group consisting of CH, C(CN), CR b and N;
Y is selected from the group consisting of CH, C(CN), CR b and N;
a is 0 or 1;
b is 0 or 1;
R 4 is selected from the group consisting of H, unsubstituted C 1 -C 6 alkyl, COR 10 , and —C(O)OR 10 ,
wherein R 10 is H or unsubstituted C 1 -C 6 alkyl;
with the proviso that when X or Y is C(CN), then a is 0;
with the proviso that when X or Y is CR b , then b is 0;
with the proviso that X and Y cannot both be C(CN);
with the proviso that X and Y cannot both be CR b ;
R b is selected from the group consisting of OR 4 , NR 4 R 5 , SR 4 , —S(O)R 4 , —S(O) 2 R 4 , —S(O) 2 NR 4 R 5 , —C(O)R 4 , —C(O)OR 4 , —C(O)NR 4 R 5 , nitro, cyano, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl,
wherein
R 4 and R 5 are each independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl
with the proviso that R 4 and R 5 , together with the atoms to which they are attached, are optionally combined to form a 5- to 7-membered substituted or unsubstituted heterocycloalkyl ring
or a salt thereof.
2. The compound of claim 1 , or a salt thereof, having a structure which is
3. The compound of claim 1 , or a salt thereof, having a structure which is
4. The compound of claim 1 , or a salt thereof, having a structure which is
5. The compound of claim 1 , or a salt thereof, having a structure which is
6. The compound of claim 1 , or a salt thereof, having a structure which is
7. The compound of claim 1 , or a salt thereof, having a structure which is
8. The compound of claim 1 , or a salt thereof, wherein R b is OR 4 , and R 4 is selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
9. The compound of claim 1 , or a salt thereof, wherein R b is OR 4 , and R 4 is substituted or unsubstituted alkyl.
10. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
11. The compound of claim 1 , or a salt thereof, wherein R b is OR 4 , and R 4 is cycloalkylsubstituted alkyl.
12. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
13. The compound of claim 1 , or a salt thereof, wherein R b is OR 4 , and R 4 is substituted or unsubstituted heteroalkyl.
14. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
15. The compound of claim 1 , or a salt thereof, wherein R b is NR 4 R 5 , and R 4 and R 5 are each independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
16. The compound of claim 1 , or a salt thereof, wherein R b is NHR 5 , and R 5 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
17. The compound of claim 1 , or a salt thereof, wherein R b is NHR 5 , and R 5 is substituted or unsubstituted heteroalkyl.
18. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
19. A pharmaceutical formulation comprising:
(a) the compound of claim 1 , or a pharmaceutically acceptable salt thereof;
(b) a pharmaceutically acceptable excipient.
20. The formulation of claim 19 , wherein the formulation is in a unit dosage form.
21. The formulation of claim 19 , wherein the formulation is for oral or topical use.
22. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
wherein R d is selected from the group consisting of H, unsubstituted C 1 -C 6 alkyl, COR 10 , and —C(O)OR 10 ,
wherein R 10 is selected from the group consisting of H and unsubstituted C 1 -C 6 alkyl.
23. The compound of claim 1 , or a salt thereof, wherein R d is H or methyl or ethyl or propyl or isopropyl or butyl or isobutyl or secbutyl or t-butyl.
24. The compound of claim 1 , or a salt thereof, wherein R d is H.
25. The compound of claim 1 , or a salt thereof, having a structure which is selected from the group consisting of
wherein R d is selected from the group consisting of H, unsubstituted C 1 -C 6 alkyl, COR 10 , and —C(O)OR 10 .
26. The compound of claim 1 , or a salt thereof, wherein R d is H or methyl or ethyl or propyl or isopropyl or butyl or isobutyl or secbutyl or t-butyl.
27. The compound of claim 1 , or a salt thereof, wherein R d is H.
28. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R d is selected from the group consisting of H, unsubstituted C 1 -C 6 alkyl and —C(O)OR 10 ,
wherein R 10 is H or unsubstituted C 1 -C 6 alkyl.
29. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R 10 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, cyclopentyl, hexyl, isohexyl and cyclohexyl.
30. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R d is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, pentyl and hexyl.
31. The compound of claim 1 , or a salt thereof, having a structure which is
32. The compound of claim 1 , or a salt thereof, having a structure which is
33. The compound of claim 1 , or a salt thereof, having a structure which is
34. The compound of claim 1 , or a salt thereof, having a structure which is
35. The compound of claim 1 , or a salt thereof, having a structure which is
36. The compound of claim 1 , or a salt thereof, having a structure which is
37. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , and R 4 is unsubstituted alkyl.
38. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , and R 4 is unsubstituted C 1 or C 2 or C 3 alkyl.
39. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , and R 4 is unsubstituted C 4 or C 5 or C 6 alkyl.
40. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , and R 4 is alkyl substituted with one or two or three halogen.
41. The compound of claim 2 , or a salt thereof, wherein R b is —O(CH 2 ) m1 OC(O)R 4d , wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R 4d is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.
42. The compound of claim 2 , or a salt thereof, wherein R b is —O(CH 2 ) m1 C(O)R 4d , wherein m1 is a number selected from 1 or 2, or 3 or 4 or 5 or 6 and R 4d is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.
43. The compound of claim 2 , or a salt thereof, wherein R b is —O(CH 2 ) m1 C(O)OR 4d , wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R 4d is H or unsubstituted.
44. The compound of claim 2 , or a salt thereof, wherein R b is —O(CH 2 ) m2 C(O)NR 4e R 4f , wherein m2 is a number selected from 1 or 2 or 3 or 4 or 5 or 6, and R 4e is H or unsubstituted alkyl, R 4f is H or unsubstituted alkyl, or R 4e and R 4f , together with the nitrogen to which they are attached, are optionally joined to form a substituted or unsubstituted 4 to 8 membered ring.
45. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , wherein R 4 is substituted or unsubstituted cycloalkyl.
46. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , wherein R 4 is unsubstituted cyclopentyl or unsubstituted cyclohexyl.
47. The compound of claim 2 , or a salt thereof, wherein R b is OR 4 , wherein R 4 is alkyl substituted with unsubstituted alkoxy.
48. The compound of claim 2 , or a salt thereof, wherein R b is —O(CH 2 ) m5 OR 30 , wherein m5 is 1 or 2 or 3 or 4 or 5 or 6 and R 30 is H or unsubstituted alkyl or unsubstituted tetrahydropyran.
49. The compound of claim 48 , or a salt thereof, wherein R 30 is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.
50. The compound of claim 2 , or a salt thereof, wherein R b is —C(O)R 4 , wherein R 4 is H or unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.
51. The compound of claim 2 , or a salt thereof, wherein R b is alkyl substituted with hydroxy.
52. The compound of claim 2 , or a salt thereof, wherein R b is alkyl substituted with carboxy or ester.
53. The compound of claim 2 , or a salt thereof, wherein R b is —(CH 2 ) m1 C(O)OR 4a , wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R 4a is H or unsubstituted alkyl.
54. The compound of claim 2 , or a salt thereof, wherein R b is —CH 2 C(O)OR 4a , wherein R 4a is H or methyl or ethyl or t-butyl.
55. The compound of claim 2 , or a salt thereof, wherein R b is alkyl substituted with amino.
56. The compound of claim 2 , or a salt thereof, wherein R b is —(CH 2 ) m7 NR 4a R 4b , wherein m7 is selected from the group consisting of 1, 2, 3, 4, 5 and 6 and R 4a is selected from the group consisting of H, unsubstituted alkyl and formyl, R 4b is selected from the group consisting of H, unsubstituted alkyl and formyl, or R 4a and R 4b , together with the nitrogen to which they are attached, are optionally joined to form a substituted or unsubstituted 4 to 8 membered ring.
57. The compound of claim 2 , or a salt thereof, wherein R b is selected from the group consisting of —NH(CH 2 ) 2 OH, —NH(CH 2 ) 2 OCH 3 , —NHCH 3 , —NHC(CH 3 ) 3 , —NH(CH 2 )Ph, and —NH(CH 2 ) 2 O(CH 2 )Ph.
58. The compound of claim 2 , or a salt thereof, wherein R b is selected from the group consisting of —N(CH 3 ) 2 , —N(CH 3 )(CH 2 ) 2 OH, —N(CH 3 )(CH 2 ) 2 OCH 3 , —NHCH 3 , —NHC(CH 3 ) 3 , —NH(CH 2 )Ph, and —NH(CH 2 ) 2 O(CH 2 )Ph.
59. The compound of claim 1 , or a salt thereof,
having a structure which is
60. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R b is OR 4
R 4 is unsubstituted C 1 or C 2 or C 3 alkyl or unsubstituted C 4 or C 5 or C 6 alkyl or
—O(CH 2 ) m1 C(O)R 4d , wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R4d is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl or
—O(CH 2 ) m5 OR 30 , wherein m5 is 1 or 2 or 3 or 4 or 5 or 6 and R 30 is unsubstituted C 1 or C 2 or C 3 or C 4 or C 5 or C 6 alkyl.
61. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R b is unsubstituted C 2 alkyl.
62. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R b is —O(CH 2 ) 3 C(O)CH 3 .
63. The compound of claim 1 , or a salt thereof, having a structure which is
wherein
R b is —O(CH 2 ) 2 OCH(CH 3 ) 2 .
64. The compound of claim 1 , or a salt thereof, having a structure which is
65. The compound of claim 1 , or a salt thereof, having a structure which is
66. The compound of claim 1 , or a salt thereof, having a structure which is