Compositions and methods for inhibition of cathepsins
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07C-337/08
C07C-049/786
출원번호
US-0253504
(2016-08-31)
등록번호
US-9873668
(2018-01-23)
발명자
/ 주소
Chaplin, David J.
Gaddale Devanna, Kishore Kumar
Parker, Erica
Pinney, Kevin G.
Song, Jiangli
Trawick, Mary Lynn
출원인 / 주소
Mateon Therapeutics, Inc.
대리인 / 주소
Shay Glenn LLP
인용정보
피인용 횟수 :
0인용 특허 :
52
초록
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.
대표청구항▼
1. A method of inhibiting an activity of a cathepsin, comprising contacting the cathepsin with a compound having a formula I, in an amount of effective to inhibit an activity of the cathepsin, or a solvate or pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting o
1. A method of inhibiting an activity of a cathepsin, comprising contacting the cathepsin with a compound having a formula I, in an amount of effective to inhibit an activity of the cathepsin, or a solvate or pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of C(═O), CH(OR6) and n is 0, 1, 2 or 3;m is 0, 1, 2 or 3;p is 0, 1, 2 or 3;R1 is hydrogen, C1-C3 alkyl, aryl and arylalkyl;R2 is hydrogen or C1-C3 alkyl;each R3 and R5 independently is selected from the group consisting of hydroxyl, C1-C3 alkyl, C1-C2 alkoxy, fluoro, and chloro;each R4 independently is selected from the group consisting of hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, halo, amino, nitro, nitroso and acyl; andR6 is selected from the group consisting of hydrogen and methyl. 2. The method of claim 1, wherein the cathepsin is cathepsin K or cathepsin L. 3. The method of claim 1, further comprising: contacting the cathepsin in vitro with the compound having formula I. 4. The method of claim 1, further comprising contacting the cathepsin in a cell with the compound having formula I. 5. The method of claim 1, wherein X is C(═O) or CH(OR6). 6. The method of claim 5, wherein X is C(═O). 7. The method of claim 1, wherein m is zero. 8. The method of claim 7, wherein n is zero and p is zero. 9. The method of claim 1, wherein n is zero and p is zero. 10. The method of claim 1, wherein m is 1. 11. The method of claim 10, wherein R4 is halo or acyl. 12. The method of claim 11, wherein R4 is substituted aryl-C(O)— or unsubstituted aryl-C(O)—. 13. The method of claim 11, wherein R4 is benzoyl. 14. The method of claim 1, wherein each of n and p, independently, is zero or one; andeach of R3 and R5, independently, is selected from the group consisting of hydroxyl, methyl, methoxy and fluoro. 15. The method of claim 1, wherein the compound having the formula I has a formula II, or a solvate or pharmaceutically acceptable salt thereof: 16. The method of claim 5, wherein X is C(═O). 17. The method of claim 16, wherein each of n, m and p, independently, is zero or one. 18. The method of claim 16, wherein n is one and R3 is selected from the group consisting of hydroxyl, methyl, methoxy, and fluoro. 19. The method of claim 16, wherein p is one and R5 is selected from the group consisting of hydroxyl, methyl, methoxy and fluoro. 20. The method of claim 16, wherein m is one and R4 is selected from the group consisting of halo and acyl. 21. The method of claim 15, wherein X is and m is zero or one. 22. A compound of claim 21, wherein each of n and p, independently, is zero or one. 23. The method of claim 15, wherein the compound is 3-benzoyl benzophenone thiosemicarbazone (3) having the formula: 24. The method of claim 15, wherein n=1, m=0, and p=1. 25. The method of claim 24, wherein R3 and R5 are fluoro. 26. The method of claim 25, wherein the compound is 1,3-bis-(4-fluorobenzoyl) benzene thiosemicarbazone (13) having the formula: 27. The method of claim 15, wherein n=0, m=1, and p=0. 28. The method of claim 27, wherein R4 is benzoyl. 29. The method of claim 28, wherein the compound is 1,3,5-Tribenzoyl benzene thiosemicarbazone (25) having the formula:
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