Rho kinase inhibitors and methods of use

摘要

The subject invention concerns materials and methods for treating diseases and disorders associated with expression of Rho associated kinases (ROCKs). Examples of diseases and disorders contemplated within the scope of the invention include, but are not limited to, oncological disorders, cardiovascular diseases, CNS disorders, and inflammatory disorders. In one embodiment, a method of the invention comprises administering a therapeutically effective amount of one or more compounds of the present invention, or a composition comprising the compounds, to a person or animal in need of treatment. The subject invention also concerns compounds that inhibit ROCKs, and compositions that comprise the inhibitor compounds of the invention. Compounds contemplated within the scope of the invention include, but are not limited to, those compounds shown in Table 5.

主权项

1. A compound having the chemical structure shown in formula I, formula IIa, formula IIb, formula III, or formula IV: wherein R1 in formula I is H, OH, S-alkyl, SO2NR2R3, NO2, CONH2, SO2-alkyl, NHC(O)-alkyl, CO2H, alkyl, cycloalkyl, alkoxy, cycloalkoxy, heterocycloalkyl, alkoxycarbonyl, heteroaryl, or aryl; R2 is H, CO, alkoxy, alkyl, aryl, heteroalkyl, heteroaryl, heterocycloalkyl, alkylcarbonyl, arylcarbonyl, or alkoxycarbonyl; R3 is H, CO, alkoxy, alkyl, aryl, heteroalkyl, heteroaryl, heterocycloalkyl, alkylcarbonyl, arylcarbonyl, or alkoxycarbonyl; any of which of R1, R2, and R3 can be optionally substituted with one or more of halogen, alkyl, alkoxy or aryl optionally substituted with alkoxy; R10 in formula IIb is H, NO2, halogen, —CH3, —SO2-alkyl, —OCH3, alkoxy, —C(O)NH-alkyl, —C(O)NH-aryl, —NHC(O)-alkyl, —NHC(O)-aryl, or aryloxy, any of which can be substituted with one or more of aryl or alkoxy, any of which can be optionally substituted with halogen, —OH, alkoxy, or aryl optionally substituted with alkoxy; R10 in formula III is H, NO2, —F, —Cl, —I, —CH3,—SO2-alkyl, —OCH3, alkoxy, —C(O)NH-alkyl, —C(O)NH-aryl, —NHC(O)-alkyl, —NHC(O)-aryl, or aryloxy, any of which can be substituted with one or more of aryl or alkoxy, any of which can be optionally substituted with halogen, —OH, alkoxy, or aryl optionally substituted with alkoxy; R10 in formula IIa and formula IV is H, NO2, —F, —Cl, —I, —CH3, —SO2-alkyl, —OCH3, alkoxy, —C(O)NH-alkyl, —C(O)NH-aryl, —NHC(O)-alkyl, —NHC(O)-aryl, or aryloxy, any of which can be substituted with one or more of aryl or alkoxy, any of which can be optionally substituted with halogen, —OH, alkoxy, or aryl optionally substituted with alkoxy; R20 in formula III is —CH3, —CO2H, heteroalkyl, aryl, or alkyl; or a pharmaceutically acceptable salt or hydrate thereof; wherein said compound of formula I comprises one or more R1, wherein said compound of formula IIa, IIb, III, or IV comprises one or more R10, and wherein said compound of formula III comprises one or more R20; or said compound having the chemical structure selected from: