| 主权项 |
1. A compound having of the formula: or a tautomer thereof or a pharmaceutically acceptable salt thereof of the compound or tautomer, wherein t is selected from the group consisting of 1 and 2; X is selected from the group consisting of O, S and NR8; R1 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, amino(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; or R1 is -L1-R13; L1 is absent or is a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R13 and the ring to which L1 is attached, wherein the atoms of the linker providing the separation are each independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur —(CR14R15)r—; R2 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; R3 is selected from the group consisting of hydrogen, carbonyloxy, (C1-10)alkoxy, carbonyl, oxycarbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, imino(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; or R3 is -L2-R18; L2 is absent or is a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R18 and the ring to which L2 is attached, wherein the atoms of the linker providing the separation are each independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; each R4 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; each R5 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; or R3 and one of R4 and R5, together with the atoms to which they are attached, form a substituted or unsubstituted ring selected from (C3-5)heterocycloalkyl and (C3-4)heteroaryl, the heterocycloalkyl moiety having 1 or 2 heteroatoms selected from N, O, and S, provided that at least one of the heteroatoms is a nitrogen atom, and the heteroaryl moiety having 1 or 2 nitrogen heteroatoms, and the ring is optionally substituted with halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero (C8-12)bicyclo aryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cyclo alkyl, (C9-12)bicyclo alkyl, hetero (C3-12)bicyclo alkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl; R6 is selected from the group consisting of hydrogen, carbonyloxy, carbonyl, oxycarbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo (C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero (C8-12)bicyclo aryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero (C3-12)cyclo alkyl, (C9-12)bicyclo alkyl, hetero (C3-12)bicyclo alkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; R7 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo (C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero (C8-12)bicyclo aryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; R8 is selected from the group consisting of hydrogen, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo (C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; R13 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; or R13 has the formula: each R14 and R15 is independently selected from the group consisting of hydrogen, halo, and (C1-3)alkyl; R18 is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, carbonyloxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, carbonyl, oxycarbonyl, amido, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted; and R19 and R20 are each independently selected from the group consisting of hydrogen, carbonyl, oxycarbonyl, amino, (C1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, carbonyl(C1-10)alkyl, thiocarbonyl(C1-10)alkyl, sulfonyl(C1-10)alkyl, sulfinyl(C1-10)alkyl, aza(C1-10)alkyl, imino(C1-10)alkyl, (C3-12)cyclo alkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl, each substituted or unsubstituted, or R19 and R20 are taken together to form a substituted or unsubstituted ring and (C1-3)alkyl optionally substituted with one or more substituents independently selected from halo, nitro, cyanohydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl; R21 and R22 are each independently selected from the group consisting of (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl, wherein the (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, carbonyl, sulfonyl, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C4-12)aryl, and hetero(C1-10)aryl; the optional carbonyl substituent is substituted with hydrogen, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C1-10)alkylamino or amino optionally substituted with (C3-12)cycloalkyl; the optional sulfonyl substituent is substituted with (C1-10)alkyl or (C1-10)alkylamino; the optional (C3-12)cycloalkyl and hetero(C3-12)cycloalkyl substituents are each optionally substituted with one or more substituents independently selected from cyano, oxo, hydroxy, (C1-10)alkoxy, amino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C3-12)cycloalkyl, and hetero(C3-12)cycloalkyl; and the optional (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, and (C1-10)azaalkyl; each R28 is independently selected from the group consisting of hydrogen, halo, (C1-3)alkyl, (C1-3)alkoxy, amino, and thio; r is selected from the group consisting of 1, 2 and 3; s is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7 and 8; and Y is selected from the group consisting of O and S; with the provisos that (a) if R1 is hydrogen, chloro, methyl, 3,4-difluorophenyl, or 1-chloro-3-methyl-1-oxopentan-3-yl-aminocarbonyl, then R6 is hydrogen, and (b) if the R3 substituent and the R4 and R5 substituents are attached to adjacent nitrogen and carbon atoms, respectively, then at least one of R3, R4, and R5 is not hydrogen. |
