Claims
- 1. A compound having the formula:
- 2. A compound according to claim 1, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)Rn, —CO2Rn, —CN, —C(O)NRnRo, —C(O)NRnORo, —C(S)Rn, —C(S)NRnRo, —NO2, —SORo, —SO2Rn, —SO2NRnRo, —SO2(NRn)(ORo), —SONRn, —SO3Rn, —PO(ORn)2, —PO(ORn)(ORo) —PO(NRnRo)(ORp), —PO(NRnRo)(NRpRq), —C(O)NRnNRoRp, or —C(S)NRnNRoRp, wherein Rn, Ro, Rp, and Rq are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the Rn, Ro, Rp, and Rq, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted,
or Z and Z1, together with the atom to which they are bonded, form a cycloalkyl or heterocycloalkyl group.
- 3. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 1 or 2, wherein Ra is substituted or unsubstituted heterocycloalkylalkyl.
- 4. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 1 or 2, wherein the alkyl moiety of the substituted or unsubstituted heterocycloalkylalkyl group is a substituted or unsubstituted saturated alkyl moiety.
- 5. A compound having the formula:
- 6. A compound according to claim 5, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(R21), —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21, and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21 and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted,
or Z and Z1, together with the atom to which they are bonded, form a cycloalkyl or heterocycloalkyl group.
- 7. A compound according to claim 5, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21). —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21, and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted.
- 8. A compound having the formula:
- 9. A compound according to claim 8, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20 , —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21), —PO(NR19R20)(N21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21, and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted,
or Z and Z1, together with the atom to which they are bonded, form a cycloalkyl or heterocycloalkyl group.
- 10. A compound according to claim 8, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21) —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21, and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted.
- 11. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 1, 5, or 8, wherein said compound, prodrug, salt, metabolite or solvate is a single stereoisomer, a mixture of stereoisomers or a racemic mixture of stereoisomers.
- 12. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 11, wherein said compound, prodrug, salt, metabolite or solvate is substantially stercoisomerically pure.
- 13. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein R1, R7, R8, and R10 are each H.
- 14. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein Z and Z1 are independently H, substituted or unsubstituted alkyl, —CO2R19, or taken together with the atom to which they are attached, form a heterocycoalkyl group, which may be optionally substituted.
- 15. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein at least one of Z or Z1 is selected from —CO2H, —CO2-alkyl, —CO2-cycloalkyl, —CO2-alkylaryl, and —CO2-alkylheteroaryl, or taken together with the atom to which they are attached form a heterocycloalkyl group , which may be optionally contain at least one O, N, S, or P and may be substituted by one or more of keto or thioketo.
- 16. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 1, 5 or 8, wherein Z and Z1 are not both H.
- 17. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 5 or 8, wherein when R3, R4, and R5 are independently H or a suitable substituent, said suitable substituent is independently selected from alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, nitro, amino, cyano, halogen, haloalkyl, hydroxyl, alkoxy, alkylenedioxy, aryloxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyloxy, heterocycloalkyloxycarbonyl, carboxyl, carbamoyl, formyl, keto, thioketo, sulfo, alkylamino, cycloalkylamino, arylamino, heterocycloalkylamino, heteroarylamino, dialkylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocycloalkylaminocarbonyl, heteroarylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, cycloalkylaminothiocarbonyl, arylaminothiocarbonyl, heterocycloalkylaminothiocarbonyl, heteroarylaminothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloalkylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylamino, cycloalkylthiocarbonylamino, arylthiocarbonylamino, heterocycloalkylthiocarbonylamino, heteroarylthiocarbonylamino, alkylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, alkylthio, arylthio and heteroarylthio, wherein any of the alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties present in the above substituents are optionally substituted.
- 18. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 17, wherein R3, R4, and R5 are independently selected from H, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, amino, cyano, halogen, haloalkyl, hydroxyl, keto, alkoxy, aryloxy, cycloalkoxy, heterocycloalkoxy, alkyloxycarbonyl, aryloxycarbonyl, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroaryl carbonyloxy, heterocycloalkyloxycarbonyl, carboxyl, alkylamino, arylamino, dialkylamino, alkylaminocarbonyl, alkylsulfonyl, and arylsulfonyl, wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl moieties of any of the above substituents may be optionally substituted by one or more of haloalkyl, nitro, amino, cyano, halogen, hydroxyl, haloalkoxy, mercapto, keto or unsubstituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, aryloxy, alkylamino, dialkylamino, alkylthio or arylthio groups.
- 19. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 8, having the formula:
- 20. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 8, having the formula:
- 21. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 8, having the formula:
- 22. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 5, having the formula:
- 23. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 8, having the formula:
- 24. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 19 to 23, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21), —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21 and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted,
or Z and Z1, together with the atom to which they are bonded, form a cycloalkyl or heterocycloalkyl group.
- 25. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 19 to 23, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21), —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21 and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted.
- 26. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein R2 is a substituted or unsubstituted alkyloxycarbonyl group, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocycloalkylcarbonyl or heteroarylcarbonyl group.
- 27. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 26, wherein R2 is a heteroarylcarbonyl group, wherein the heteroaryl moiety is a five-membered heterocycle having from one to three heteroatoms selected from O, N, and S.
- 28. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 27, wherein R2 is heteroarylcarbonyl, where the heteroaryl moiety is a five-membered heterocycle having at least one nitrogen heteroatom and at least one oxygen heteroatom.
- 29. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 27, wherein R2 is heteroarylcarbonyl, where the heteroaryl moiety is unsubstituted or substituted 1,2-oxazolyl, 1,3-oxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, or 1,2,5-oxadiazolyl.
- 30. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 27, wherein R2 is heteroarylcarbonyl, where the heteroaryl moiety is selected from unsubstituted and monomethyl-substituted 1,2,4-oxadiazolyl.
- 31. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 28, wherein R2 is heteroarylcarbonyl, where the heteroaryl moiety is selected from 3-isoxazolyl and 5-isoxazolyl, each unsubstituted or substituted with one or two substituents selected from methyl groups and halogens.
- 32. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein R6 is H or a substituted or unsubstituted lower alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl group, a straight-chain saturated hydrocarbon moiety or an unsaturated hydrocarbon moiety.
- 33. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 32, wherein R6 is H, ethyl, 2-propyn-1-yl, methylcyclohexyl, or substituted or unsubstituted benzyl, wherein the phenyl moiety of the substituted benzyl has one or more substituents independently selected from lower alkyl, lower alkoxy and halogen.
- 34. The compound, prodrug, pharmaceutically acceptable salt, pharmaceuticaly active metabolite, or pharmaceutically acceptable salt according to any one of claims 1 or 5 to 10, wherein when p is 0, m is 0.
- 35. The compound, prodrug, pharmaceutically acceptable salt, pharmaceuticaly active metabolite, or pharmaceutically acceptable salt according to any one of claims 1 or 5 to 10, wherein m is 1 and p is 1 or 2.
- 36. The compound, prodrug, pharmaceutically acceptable salt, pharmaceuticaly active metabolite, or pharmaceutically acceptable salt according to any one of claims 1 or 5 to 10, wherein m is 1 and p is 1.
- 37. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 5 to 10, wherein R9 is selected from —CH2CH2C(O)NH2; —CH2CH2C(O)NH-alkyl; —CH2NHC(O)CH3; and
- 38. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 37, wherein R9 is
- 39. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 1 or 5 to 10, wherein Z1 is H or lower alkyl and Z is substituted or unsubstituted ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, (2,2-dimethylpropyl)-oxycarbonyl, benzyloxycarbonyl, pyridylmethyleneoxycarbonyl, cyclobutyloxycarbonyl, cyclopentyloxycarbonyl, cyclohexyloxycarbonyl,, cycloheptyloxycarbonyl, or Z taken together with Z1 and the atom to which they are
- 40. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 20, wherein Rx is selected from H, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, nitro, amino, cyano, halogen, haloalkyl, hydroxyl, alkoxy, alkylenedioxy, aryloxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyloxy, heterocycloalkyloxycarbonyl, carboxyl, carbamoyl, formyl, keto, thioketo, sulfo, alkylamino, cycloalkylamino, arylamino, heterocycloalkylamino, heteroarylamino, dialkylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocycloalkylaminocarbonyl, heteroarylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, cycloalkylaminothiocarbonyl, arylaminothiocarbonyl, heterocycloalkylaminothiocarbonyl, heteroarylaminothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloalkylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylamino, cycloalkylthiocarbonylamino, arylthiocarbonylamino, heterocycloalkylthiocarbonylamino, heteroarylthiocarbonylamino, alkylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, alkylthio, arylthio and heteroarylthio, wherein any of the alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties present in the above substituents may be further substituted with one or more substituents selected from nitro, amino, cyano, halogen, haloalkyl, hydroxyl, keto and unsubstituted alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, and aryloxy.
- 41. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 21, 22 or 23, wherein Ry is selected from H, alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, nitro, amino, cyano, halogen, haloalkyl, hydroxyl, alkoxy, alkylenedioxy, aryloxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, alkylcarbonyl, alkyloxycarbonyl, alkylcarbonyloxy, arylcarbonyl, arylcarbonyloxy, aryloxycarbonyl, cycloalkylcarbonyl, cycloalkylcarbonyloxy, cycloalkyoxycarbonyl, heteroarylcarbonyl, heteroarylcarbonyloxy, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkylcarbonyloxy, heterocycloalkyloxycarbonyl, carboxyl, carbamoyl, formyl, keto, thioketo, sulfo, alkylamino, cycloalkylamino, arylamino, heterocycloalkylamino, heteroarylamino, dialkylamino, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocycloalkylaminocarbonyl, heteroarylaminocarbonyl, dialkylaminocarbonyl, alkylaminothiocarbonyl, cycloalkylaminothiocarbonyl, arylaminothiocarbonyl, heterocycloalkylaminothiocarbonyl, heteroarylaminothiocarbonyl, dialkylaminothiocarbonyl, alkylsulfonyl, arylsulfonyl, alkylsulfenyl, arylsulfenyl, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocycloalkylcarbonylamino, heteroarylcarbonylamino, alkylthiocarbonylamino, cycloalkylthiocarbonylamino, arylthiocarbonylamino, heterocycloalkylthiocarbonylamino, heteroarylthiocarbonylamino, alkylsulfonyloxy, arylsulfonyloxy, alkylsulfonylamino, arylsulfonylamino, mercapto, alkylthio, arylthio and heteroarylthio, wherein any of the alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl moieties present in the above substituents may be further substituted with one or more substituents selected from nitro, amino, cyano, halogen, haloalkyl, hydroxyl, keto and unsubstituted alkyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, alkoxy, and aryloxy.
- 42. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 19, having the formula:
- 43. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 20, having the formula:
- 44. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 21, having the formula:
- 45. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 22, having the formula:
- 46. A compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 23, having the formula:
- 47. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 42 to 46, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19, —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21), —PO(NR19R20)(NR21R22), —C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21, and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted,
or Z and Z1, together with the atom to which they are bonded, form a cycloalkyl or heterocycloalkyl group.
- 48. The compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to any one of claims 42 to 46, wherein Z and Z1 are independently H, F, a unsubstituted or substituted alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group, —C(O)R19, —CO2R19, —CN, —C(O)NR19R20, —C(O)NR19OR20, —C(S)R19, —C(S)NR19R20, —NO2, —SOR20, —SO2R19, —SO2NR19R20, —SO2(NR19)(OR20), —SONR19, —SO3R19 , —PO(OR19)2, —PO(OR19)(OR20), —PO(NR19R20)(OR21), —PO(NR19R20)(NR21R22), C(O)NR19NR20R21, or —C(S)NR19NR20R21, wherein R19, R20, R21 and R22 are independently H, a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, heterocycloalkyl group, acyl group or thioacyl group, or wherein any two of the R19, R20, R21, and R22, taken together with the atoms to which they are bonded, form a heterocycloalkyl group, which may be optionally substituted.
- 49. The compound according to any one of claims 1 or 5 to 10, having antipicornaviral activity corresponding to an EC50 less than or equal to 100 μM in an H1-HeLa cell culture assay.
- 50. A pharmaceutical composition comprising:
a therapeutically effective amount of at least one antipicornaviral agent selected from compounds, prodrugs, pharmaceutically acceptable salts, pharmaceutically active metabolites, and pharmaceutically acceptable solvates defined in any one of claims 1 or 5 to 10; and a pharmaceutically acceptable carrier, diluent, vehicle, or excipient.
- 51. 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, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate defined in any one of claims 1 or 5 to 10.
- 52. The method according to claim 51, wherein the at least one compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate is administered orally.
- 53. 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, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate defined in any one of claims 1 or 5 to 10.
- 54. The method according to claim 53, wherein the at least one compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate is administered orally.
- 55. 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, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate defined in any one of claims 1 or 5 to 10.
- 56. The method as defined in claim 55, wherein the picornaviral 3C protease is a rhinoviral protease.
- 57. A compound having the formula:
- 58. The compound according to claim 57, having the formula:
- 59. A compound having the formula:
- 60. A stereoisomer of the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59, having the formula:
- 61. A stereoisomer of the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59, having the formula:
- 62. A stereoisomer of the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59, having the formula:
- 63. A stereoisomer of the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59, having the formula:
- 64. A pharmaceutical composition comprising:
a therapeutically effective amount of an antipicornaviral agent selected from the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59 or 63; and a pharmaceutically acceptable carrier, diluent, vehicle, or excipient.
- 65. A method of inhibiting the activity of a picornaviral 3C protease, comprising contacting the picornaviral 3C protease with an effective amount of the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate according to claim 59 or 63.
- 66. The method as defined in claim 65, wherein the picornaviral 3C protease is a rhinoviral protease.
- 67. 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 the compound, prodrug, pharmaceutically acceptable salt, pharmaceutically active metabolite, or pharmaceutically acceptable solvate as defined in claim 59 or 63.
- 68. A compound selected from:
Parent Case Info
[0001] This application claims benefit of U.S. Provisional Patent Application No. 60/168,986, filed Dec. 3, 1999 and U.S. Provisional Patent Application No. 60/192,052, filed Mar. 24, 2000, the disclosures of which are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60168986 |
Dec 1999 |
US |
|
60192052 |
Mar 2000 |
US |