Claims
- 1. A compound of the formula (I):
- 2. A compound of claim 1, wherein R1 is H or F, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 3. A compound of claim 1, wherein R20 is H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, —OR17, —SR17, —NR17R18, —NR19NR17R18, or —NR17OR18, wherein R17, R18, and R19 independently are H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 4. A compound of claim 3, wherein R20 is the alkyl group —C(R41)(R42)NR43R44,
- 5. A compound of claim 4, wherein at least one of R43 or R44 is —C(O)SR45 or —C(O)OR45, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 6. A compound of claim 5, wherein R45 is an alkyl group, a cycloalkyl group, an aryl group, a heterocycloalkyl group, or a heteroaryl group, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 7. A compound of claim 6, wherein R45 is a C1-C10 alkyl group or a cycloalkyl group, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 8. A compound of claim 1, wherein at least one of R2 or R5 is
- 9. A compound according to claim 8, wherein D1 is —OR25, ═O, ═S, ≡N, ═NR25, or —NR25R26, wherein R25 and R26 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, or, together with the nitrogen atom to which they are bonded, form a heterocycloalkyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 10. A compound according to claim 9, wherein D1 is ═O; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 11. A compound according to claim 8, wherein A1 is C, CH, S, or S(O); or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 12. A compound according to claim 11, wherein A1 is C; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 13. A compound according to claim 8, wherein B1 is NR17R18, wherein R17 and R18 are independently H, an allyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 14. A compound according to claim 1, wherein at least one of R2 or R5 is
- 15. A compound according to claim 14, wherein D2 is —OR25, ═O, ═S, ≡N, ═NR25, or —NR25R26, wherein R25 and R26 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, or, together with the atom(s) to which they are bonded, form a heterocycloalkyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 16. A compound according to claim 15, wherein D2 is ═O; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 17. A compound according to claim 14, wherein A2 is C, CH, S, or S(O); or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 18. A compound according to claim 17, wherein A2 is C; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 19. A compound according to claim 14, wherein B2 is —NR17R18, wherein R17 and R18 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, or an acyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 20. A compound according to claim 1, wherein A1 is C, CH, S, or S(O) or wherein A2 is C, CH, S, or S(O); or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 21. A compound according to claim 1, wherein Z and Z1 are independently H, an aryl group, or a heteroaryl group, —C(O)R21, —CO2R21, —CN, —C(O)NR21R22, —C(O)NR21OR22, —C(S)R21, —C(S)NR21R22, —NO2, —SOR21, —SO2R21, —SO2NR21R22, —SO(NR21)(OR22), —SONR21, —SO3R21, —C(O)NR21NR22R23, or —C(S)NR21NR22R23;
wherein R21, R22, and R23 are independently H, an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, or a thioacyl group, or wherein any two of R21, R22, and R23, together with the atom(s) to which they are bonded, form a heterocycloalkyl group; or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 22. A compound according to claim 1, wherein M is O.
- 23. A compound having the formula X:
- 24. A compound according to claim 23, wherein R66 is the acyl group —C(O)OR68 or the acyl group —C(O)SR68, wherein R68 is an alkyl group, a cycloalkyl group, an aryl group, a heterocycloalkyl group, or a heteroaryl group, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 25. A compound according to claim 4, having the formula II:
- 26. A compound according to claim 4, having the formula III:
- 27. A compound of formula (IV):
- 28. A composition comprising at least one compound of formula II:
- 29. A pharmaceutical composition comprising:
(a) a therapeutically effective amount of at least one compound as defined in claim 1 or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof; and (b) a pharmaceutically acceptable carrier, diluent, vehicle, or excipient.
- 30. A method of treating a mammalian disease condition mediated by picornaviral protease activity, comprising: administering to a mammal in need thereof a therapeutically effective amount of at least one compound as defined in claim 1 or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 31. A method of inhibiting the activity of a picornaviral 3C protease, comprising: contacting the picornaviral 3C protease with an effective amount of at least one compound as defined in claim 1 or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 32. A method of inhibiting the activity of a rhinoviral protease, comprising: contacting the rhinoviral protease with an effective amount of at least one compound as defined in claim 1 or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof.
- 33. A compound according to claim 1, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof, wherein said antipicornaviral activity is antirhinoviral activity.
- 34. A compound according to claim 1, or a pharmaceutically acceptable prodrug, salt, active metabolite, or solvate thereof, wherein said antipicornaviral activity is anticoxsackieviral activity.
RELATED APPLICATION DATA
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 08/825,331, filed Mar. 28, 1997, which application is entirely incorporated herein by reference.
[0002] Additionally, this application relates to U.S. patent application Ser. No. 08/850,398, filed May 2, 1997, and U.S. Provisional Patent Appln. No. 60/046,204, filed May 12, 1997. Each of these U.S. patent applications relates to antipicornaviral compounds, compositions containing them, and methods for their production and use. Each of these applications also is entirely incorporated herein by reference. This application also relates to a concurrently filed U.S. patent application entitled “Antipicornaviral Compounds and Methods for Their Use and Preparation,” U.S. patent application Ser. No. ______, filed in the names of inventors Stephen E. Webber, Peter S. Dragovich, Thomas J. Prins, Ethel S. Littlefield, Joseph T. Marakovits, and Robert E. Babine (Attorney Docket No. 1074.0175). This concurrently filed application also is entirely incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
|
60046204 |
May 1997 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09421560 |
Oct 1999 |
US |
Child |
09947381 |
Sep 2001 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
08825331 |
Mar 1997 |
US |
Child |
09421560 |
Oct 1999 |
US |