Claims
- 1. A compound of the formula
- 2. The compound of claim 1, wherein Y is
- 3. The compound as defined in claim 2, wherein L is a linker that places the R1 group at a distance of about 6 Å-15 Å from the —CH(R2)—CO—NH—Y group.
- 4. The compound defined in claim 3, wherein the distance is about 7 Å-12 Å.
- 5. The compound defined in claim 3, where the distance is about 8 Å-10 Å.
- 6. The compound of claim 2, wherein L is is selected from the group consisting of —(CH2)m—O—(CH2)n—; —(CH2)m—NR—(CH2)m—; —(CH2)m—NRCONR—(CH2)n—; (CH2)m—NRCOO—(CH2)n—; —(CH2)m—CONR—(CH2)n—; —(CH2)m—NRCO—(CH2)n—; —(CH2)m—NRSO2—(CH2)n—; —(CH2)m—CO—(CH2)n—; —(CH2)m—NRCONRSO2—(CH2)n—; —(CH2)m—NRCONRCO—(CH2)n—; —(CH2)m—SO2—(CH2)n—; —(CH2)m—SO2CH2CO—(CH2)n—; —(CH2)m—SO2NR—(CH2)n—; and, —(CH2)m—SCH2CO—(CH2)n— where m and n are each 0, 1, 2, 3, 4, or 5, and wherein R is each independently hydrogen, C1-C5 alkyl, C1-C5 hydroxyalkyl, or C1-C5 alkylhalide.
- 7. The compound of claim 6 where L is —(CH2)m—CONR—(CH2)n— and m and n are each 0, 1, 2, 3, or 5.
- 8. The compound of claim 6 where L is —(CH2)m—NRCO—(CH2)n— and m and n are each 0, 1, 2, 3, or 5.
- 9. The compound of claim 6 where L is —(CH2)m—NRSO2—(CH2)n— and m and n are each 0, 1, 2, 3, or 5.
- 10. The compound of claim 6 where L is —(CH2)m—SO2NR—(CH2)n— and m and n are each 0, 1, 2, 3, or 5.
- 11. The compound of claim 2 wherein L is -Z-(CH2)m—Ar—(CH2)n— where Z is —C(═O)NH—, —NHC(═O)—, or —SO2NH—; m and n are each 0, 1, 2, or 3; and Ar is a 5 or 6 membered arylene or heteroarylene.
- 12. The compound defined in claim 2 selected from
- 13. The compound of claim 12, wherein X is —(CO)—.
- 14. The compound of claim 12, wherein n is 1.
- 15. The compound of claim 12, wherein R1 is optionally substituted aryl or optionally substituted heteroaryl.
- 16. The compound of claim 13, wherein R1 is chosen from optionally substituted phenyl, optionally substituted naphthyl, optionally substituted pyridinyl, optionally substituted quinolinyl, optionally substituted thiophenyl, optionally substituted oxazolyl, optionally substituted 2,3-dihydro-benzo[b]thiophen-2-yl, and optionally substituted quinoxalinyl.
- 17. The compound defined in claim 14, where R1 is dimethylphenyl, tolyl methyl, quinoxalinyl, tolyl cyclopentyl, morpholinylpyridyl, napthalenyl, chloro benzo[b]thienyl, amino dichlorophenyl, quinolinyl, phenyloxazolyl, tolyl, thienyl, trifluoro acetyl tetrahydro isoquinolinyl, pyridyl thienyl, fluoro chloro carboxy phenyl, hydroxy carboxy phenyl, benzooxazolyl, or quinoxalinyl amino phenyl.
- 18. The compound of claim 16, wherein R2 is chosen from optionally substituted thiophenyl, optionally substituted phenyl, optionally substituted pyridinyl, and optionally substituted benzofuranyl.
- 19. The compound of claim 18, wherein R2 is selected from the group consisting of H, thienyl, preferably 2-thienyl, alkyl thienyl, preferably 3-methyl 2-thienyl, phenoxy, preferably 4-phenoxy, phenyl, alkylphenyl, preferably 4-isopropyl phenyl, acetylaminophenyl, preferably 4-acetylaminophenyl, pyridyl, preferably 3-pyridyl, and benzooxazole.
- 20. The compound of claim 2 selected from the group consisting of:
- 21. The compound defined in claim 20 selected from the group consisting of
- 22. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1; and a pharmaceutically acceptable excipient.
- 23. A method of treating an animal having a disease that would benefit from treatment by administration of a caspase-1 inhibitor, comprising administering to said animal a therapeutically effective amount of a compound of claim 1.
- 24. A method of claim 23 wherein the disease is inflammation, rheumatoid arthritis, or sepsis.
- 25. A method of inhibiting caspase-1, the method comprising administering to a patient in need of inhibition of caspase-1, a therapeutically effective amount of a compound of claim 1.
- 26. A method of preserving or storing a solution of mammalian organs or tissues or a growth media for mammalian or yeast cells, the method comprising admixing with said solution or growth media, an amount of the compound of claim 1 effective to reduce apoptotic cell death in said organs, tissues or cells.
- 27. An isolated crystalline apo-human caspase-1.
Parent Case Info
[0001] This application claims priority to U.S. provisional application No. 60/386,501, filed Jun. 5, 2002, which is incorporated herein by this reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60386501 |
Jun 2002 |
US |