USRE47302EActiveUtilityPatentIndex 50
Peptide epoxyketone immunoproteasome inhibitors
Est. expiryMar 14, 2033(~6.7 yrs left)· nominal 20-yr term from priority
C07K 5/0827C07D 407/12C07K 5/0823C07K 5/0812C07D 413/12C07K 5/081C07K 5/0808C07K 5/06034C07K 5/06147C07K 5/06078A61K 38/06C07K 5/06121C07K 5/06191C07K 5/0821C07K 5/06173C07K 5/06069A61P 21/04A61P 5/00C07K 5/06026A61P 13/12C07K 5/06113C07K 5/0806C07D 303/32A61P 1/00C07D 405/12A61P 29/00A61P 31/04A61P 7/06A61P 17/06A61P 7/00A61K 38/00C07K 5/0202A61P 19/02C07D 409/12C07K 5/0606A61P 9/10A61P 43/00C07K 5/0205A61P 31/06A61P 25/00A61P 1/04A61P 37/02A61P 3/10A61P 17/00A61P 37/08A61P 11/06C07K 5/06139A61P 37/00A61P 11/00
50
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Cited by
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References
31
Claims
Abstract
Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A compound of Formula (X):
wherein:
m and n each independently are 0, 1 or 2, and m+n=2, 3, or 4;
p is 0 or 1;
q is 0, 1, or 2;
K is selected from the group consisting of CR 5 R 6 , NR 7 , N(C═O)OR 7 , —NH—(C═O)—, O, S, SO, and SO 2 ;
E is N or CR 7 ;
R 1 is selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, and 3-6 membered heterocycloalkyl, wherein R 1 is optionally substituted with one or more substituents selected from the group consisting of halo, OR 7 , SR 7 , N(R 7 ) 2 , CN, and (C═O)N(R 7 ) 2 ;
R 2 is C 1-2 alkylene-G or (C═O)-G; wherein G is selected from the group consisting of aryl, heteroaryl, and pyridinone, with the proviso that when R 2 is CH 2 phenyl, the phenyl is substituted with one or more substituents selected from the group consisting of OR 7 , halo, C 1-3 alkyl, OCF 3 , SO 2 R 7 , (C═O)N(R 7 ) 2 , CN, and SO 2 N(R 7 ) 2 ;
R 3 is non-aromatic and selected from the group consisting of C 3-7 cycloalkyl, C 3-7 cycloalkenyl, a 3-7 membered heterocycloalkyl, and a 3-7 membered heterocycloalkenyl, wherein R 3 is optionally substituted with one or more substituents selected from the group consisting of halo, ═O, OR 7 , SR 7 , N(R 7 ) 2 , O(C═O)N(R 7 ) 2 , and C 1-6 alkyl;
R 4 is H or C 1-3 alkyl;
R 5 and R 6 are each independently selected from the group consisting of H, OH, halo, C 1-3 alkyl, and CF 3 , or R 5 and R 6 together with the carbon to which they are attached form C═O or
wherein W is O or NR 7 , and r is 1, 2 or 3; and
each R 7 is independently H or C 1-6 alkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , having the formula:
wherein:
K is CH(OH) or O;
E is N or CH;
R 1 is CH 3 , CH 2 OH, CH(OH)CH 3 , or CH 2 CN;
R 2 is
3. The compound of claim 2 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. A compound having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 3 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 2 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 6 1 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein K is O.
9. The compound of claim 1 , wherein E is N.
10. The compound of claim 1 , wherein
is selected from the group consisting of:
11. The compound of claim 1 , wherein R 1 is C 1-3 alkyl.
12. The compound of claim 1 , wherein R 2 is CH 2 -heteroaryl or CH 2 -aryl.
13. The compound of claim 12 , wherein R 2 is selected from the group consisting of:
14. The compound of claim 1 , wherein R 3 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, pyrrolidinonyl, dihydropyranyl or and dihydrofuranyl.
15. The compound of claim 1 , wherein:
is selected from the group consisting of:
R 1 is selected from the group consisting of CH 3 , CH 2 OH, CF 3 , CH(OH)CH 3 , CH 2 CN, CH 2 CH 3 , CH 2 CH═CH 2 , CH 2 C≡CH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl oxetanyl, tetrahydrofuranyl, and piperadinyl;
R 2 is selected from the group consisting of:
R 3 is selected from the group consisting of:
R 4 is selected from the group consisting of methyl, ethyl, and hydrogen.
16. The compound of claim 1 , wherein
is selected from the group consisting of:
17. The compound of claim 1 , wherein R 1 is CH 3 , CH 2 OH, CH(OH)CH 3 , or CH 2 CN.
18. The compound of claim 1 , wherein R 2 is selected from the group consisting of:
19. The compound of claim 1 , wherein R 3 is selected from the group consisting of:
20. The compound of claim 12 , wherein the heteroaryl is a thiophene.
21. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
22. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
28. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
29. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
30. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.
31. The compound of claim 1 having a structure of
or a pharmaceutically acceptable salt thereof.Cited by (0)
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