Claims
- 1. A compound comprising an amino acid sequence of from 1 to 4 amino acid residues having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein said amino acid sequence substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3.
- 2. The compound according to claim 1 having the formula:
- Z-Q.sub.2 -Asp-Q.sub.1
- where
- Z is an N-terminal protecting group;
- Q.sub.2 is 0 to 3 amino acids such that the sequence Q.sub.2 -Asp substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3;
- and
- Q.sub.1 is an electronegative leaving group.
- 3. The compound according to claim 2 wherein Z is C.sub.1 -C.sub.6 alkyl, benzyl, acetyl, C.sub.1 -C.sub.6 alkoxycarbonyl, benzyloxycarbonyl or C.sub.1 -C.sub.6 alkyl carbonyl.
- 4. The compound according to claim 2 wherein Z is t-butoxycarbonyl, acetyl or benzyloxycarbonyl.
- 5. The compound according to claim 2 wherein Q.sub.1 is an aldehyde, a diazomethyl ketone or a halomethyl ketone.
- 6. The compound according to claim 2 wherein Q.sub.1 is fluoromethyl ketone.
- 7. The compound according to claim 2 wherein Q.sub.2 is 1 amino acid residue.
- 8. The compound according to claim 2 wherein Q.sub.2 is His, Phe, Pro or Tyr.
- 9. A pharmaceutical composition comprising a physiologically acceptable carrier and a compound of the formula:
- Z-Q.sub.2 -Asp-Q.sub.1
- where
- Z is an N-terminal protecting group;
- Q.sub.2 is 0 to 3 amino acids such that Q.sub.2 -Asp substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3;
- and
- Q.sub.1 is an electronegative leaving group.
- 10. The composition according to claim 9 wherein Z is C.sub.1 -C.sub.6 alkyl, benzyl, acetyl, C.sub.1 -C.sub.6 alkoxycarbonyl, benzyloxycarbonyl or C.sub.1 -C.sub.6 alkoxycarbonyl, benzyloxycarbonyl or C.sub.1 -C.sub.6 alkyl carbonyl.
- 11. The composition according to claim 9 wherein Z is t-butoxycarbonyl, acetyl or benzyloxycarbonyl.
- 12. The composition according to claim 9 wherein Q.sub.1 is an aldehyde, a diazomethyl ketone or a halomethyl ketone.
- 13. The composition according to claim 9 wherein Q.sub.1 is fluoromethyl ketone.
- 14. The composition according to claim 9 wherein Q.sub.2 is 1 amino acid residue.
- 15. The composition according to claim 9 wherein Q.sub.2 is His, Phe, Pro or Tyr.
- 16. A method of inhibiting IL-1.beta. protease activity in a mammal in need of such treatment comprising administering to said mammal an effective inhibitory amount of a compound of the formula:
- Z-Q.sub.2 -Asp-Q.sub.1
- where
- Z is an N-terminal protecting group;
- Q.sub.2 is 0 to 3 amino acids such that the sequence Q.sub.2 -Asp substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3;
- and
- Q.sub.1 is an electronegative leaving group.
- 17. The method according to claim 16 wherein Z is C.sub.1 -C.sub.6 alkyl, benzyl, acetyl, C.sub.1 -C.sub.6 alkoxycarbonyl, benzyloxycarbonyl or C.sub.1 -C.sub.6 alkyl carbonyl.
- 18. The method according to claim 16 wherein Z is t-butoxycarbonyl, acetyl or benzyloxycarbonyl.
- 19. The method according to claim 16 wherein Q.sub.1 is an aldehyde, a diazomethyl ketone or a halomethyl ketone.
- 20. The method according to claim 16 wherein Q.sub.2 is 1 amino acid residue.
- 21. The method according to claim 16 wherein Q.sub.2 is His, Phe, Pro or Tyr.
- 22. The method according to claim 16 wherein Q.sub.1 is an aldehyde and inhibiting is reversibly inhibiting.
- 23. The method according to claim 16 wherein Q.sub.1 is fluoromethyl ketone and inhibiting is irreversibly inhibiting.
- 24. A method of treating inflammation or treating an autoimmune disease in a mammal in need of such treatment comprising administering to said mammal an effective amount of a compound of the formula:
- Z-Q.sub.2 -Asp-Q.sub.1
- where
- Z is an N-terminal protecting group;
- Q.sub.2 is 0 to 3 amino acids such that the sequence Q.sub.2 -Asp substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3; and
- Q.sub.1 is an electronegative leaving group.
- 25. The method according to claim 24 wherein Z is C.sub.1 -C.sub.6 alkyl, benzyl, acetyl, C.sub.1 -C.sub.6 alkyl carbonyl.
- 26. The method according to claim 24 wherein Z is t-butoxycarbonyl, acetyl or benzyloxycarbonyl.
- 27. The method according to claim 24 wherein Q.sub.1 is an aldehyde, a diazomethyl ketone or a halomethyl ketone.
- 28. The method according to claim 24 wherein Q.sub.2 is 1 amino acid residue.
- 29. The method according to claim 24 wherein Q.sub.2 is His, Phe, Pro or Tyr.
- 30. A compound selected from the group consisting of Boc-Asp-CH.sub.2 F, Boc-His-Asp-CH.sub.2 F, Boc-Phe-Asp-CH.sub.2 F, Boc-Pro-Asp-CH.sub.2 F, Boc-Tyr-Asp-CH.sub.2 F, Ac-His-Asp-CH.sub.2 F, Ac-Phe-Asp-CH.sub.2 F, Ac-Pro-Asp-CH.sub.2 F, Ac-Tyr-Asp-CH.sub.2 F, Cb.sub.3 -His-Asp-CH.sub.2 F, Cb.sub.3 -Phe-Asp-CH.sub.2 F, Cb.sub.3 -Pro-Asp-CH.sub.2 F, and Cb.sub.3 -Tyr-Asp-CH.sub.2 F wherein Boc is t-butoxycarbonyl, Ac is acetyl and Cb.sub.3 is benzyloxycarbonyl.
Parent Case Info
This application is a division of U.S. application Ser. No. 08/440,179, now U.S. Pat. No. 5,756,465, filed May 12, 1995 which is a division of U.S. application Ser. No. 08/203,716, now U.S. Pat. No. 5,416,013, filed Feb. 28, 1994 which is a continuation of U.S. application Ser. No. 07/750,644, filed on Aug. 30, 1991, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07/505,298, filed Apr. 4, 1990, now abandoned, and U.S. application Ser. No. 07/656,759, filed Feb. 13, 1991, now abandoned.
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Divisions (2)
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Number |
Date |
Country |
Parent |
440179 |
May 1995 |
|
Parent |
203716 |
Feb 1994 |
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Continuations (1)
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Number |
Date |
Country |
Parent |
750644 |
Aug 1991 |
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Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
505298 |
Apr 1990 |
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Parent |
656759 |
Feb 1991 |
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