Novel rho kinase inhibitors and methods of use

A composition comprising 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 IIa, formula IIb, formula III, and formula IV 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;
• R20 in formula III is —CH3, —CO2H, heteroalkyl, aryl, or alkyl;
• or a pharmaceutically acceptable salt or hydrate thereof;
• wherein said compound can comprise one or more R1, wherein said compound can comprise one or ore R10, and wherein said compound can comprise one or more R20;
• or
• said compound having the chemical structure selected from:

A method for treating a person or animal having a disorder or condition associated with aberrant or excessive ROCK activity or interaction in a cell or decreased apoptosis of a cell, or a disorder or condition associated with inhibition or downregulation of apoptosis of a cell, wherein the method comprises administering to the person or animal an effective amount of one or more compounds 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 IIa, formula IIb, formula III, and formula IV 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;
• R20 in formula III is —CH3, —CO2H, heteroalkyl, aryl, or alkyl;
• or a pharmaceutically acceptable salt or hydrate thereof;
• wherein said compound can comprise one or more R1, wherein said compound can comprise one or more R10, and wherein said compound can comprise one or more R20;
• or
• said compound having the chemical structure selected from:
• or a composition comprising said one or more compounds.

A method for inhibiting ROCK activity in a cell, comprising contacting the cell with an effective amount of one or more compounds 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, 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 IIa, formula IIb, formula III, and formula IV 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;
• R20 in formula III is —CH3, heteroalkyl, aryl, or alkyl;
• or a pharmaceutically acceptable salt or hydrate thereof;
• wherein said compound can comprise one or more R1, wherein said compound can comprise one or more R10, and wherein said compound can co rise one or more R20;
• or
• said compound having the chemical structure selected from:
• or a composition comprising said one or more compounds.