Compositions and methods for inhibition of cathepsins
View Patent ↗This invention is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin K or cathepsin L, will be therapeutically useful.
1. A compound of formula I:
or a solvate or pharmaceutically acceptable salt thereof, wherein
X is selected from the group consisting of C(═O), CH(OR 6 ) and
n is 0, 1, 2 or 3;
m is 0, 1, 2 or 3;
p is 0, 1, 2 or 3;
R 1 is hydrogen, C 1 -C 3 alkyl, aryl and arylalkyl;
R 2 is hydrogen or C 1 -C 3 alkyl;
each R 3 and R 5 independently is selected from the group consisting of hydroxyl, C 1 -C 3 alkyl, C 1 -C 2 alkoxy, fluoro, and chloro;
each R 4 independently is selected from the group consisting of hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halo, amino, nitro, nitroso and acyl; and
R 6 is selected from the group consisting of hydrogen and methyl.
2. The compound of claim 1 , wherein X is C(═O) or CH(OR 6 ).
3. The compound of claim 2 , wherein X is C(═O).
4. The compound of claim 1 , wherein m is zero.
5. The compound of claim 4 , wherein n is zero and p is zero.
6. The compound of claim 1 , wherein n is zero and p is zero.
7. The compound of claim 1 wherein m is 1.
8. The compound of claim 7 , wherein R 4 is halo or acyl.
9. The compound of claim 8 , wherein R 4 is substituted aryl-C(O)— or unsubstituted aryl-C(O)—.
10. The compound of claim 8 , wherein R 4 is benzoyl.
11. The compound of claim 1 , wherein
each of n and p, independently, is zero or one; and
each of R 3 and R 5 , independently, is selected from the group consisting of hydroxyl, methyl, methoxy and fluoro.
12. The compound of claim 1 , having formula II, or a solvate or pharmaceutically acceptable salt thereof:
13. The compound of claim 12 , wherein X is C(═O).
14. The compound of claim 13 , wherein each of n, m and p, independently, is zero or one.
15. The compound of claim 13 , wherein n is one and R 3 is selected from the group consisting of hydroxyl, methyl, methoxy, and fluoro.
16. The compound of claim 13 , wherein p is one and R 5 is selected from the group consisting of hydroxyl, methyl, methoxy and fluoro.
17. The compound of claim 13 , wherein m is one and R 4 is selected from the group consisting of halo and acyl.
18. The compound of claim 12 , wherein X is
and m is zero or one.
19. The compound of claim 18 , wherein each of n and p, independently, is zero or one.
20. The compound of claim 1 , having formula Ill, or a solvate or pharmaceutically acceptable salt thereof: