Inhibitors of Rho Associated Coiled-Coil Containing Protein Kinase

A compound having the formula I:

• wherein:
• R1 is selected from the group consisting of lower alkyl, substituted lower alkyl, C3-C6 cycloalkyl, substituted C3-C6 cycloalkyl, R10R11N(CR12R13)c—, R10O(CR12R13)c—, W(CR12R13)d— and R10R11N—C(═O)—(CR12R13)c—;
• each R10 is independently selected from H, lower alkyl, and C3-C6 cycloalkyl;
• each R11 is independently selected from H, lower alkyl, and C3-C6 cycloalkyl;
• each R12 is independently selected from H and lower alkyl;
• each R13 is independently selected from H and lower alkyl;
• additionally or alternatively, an R12 and an R13 attached to the same carbon atom may be taken together to form a C3-C6 cycloalkyl group;
• W is a 3- to 7-membered heterocyclic ring having 1 to 3 ring heteroatoms;
• c is 2 to 4;
• d is 1 to 4;
• R2 is selected from the group consisting of aryl, heteroaryl, aralkyl, and heterocyclyl, each of which may be unsubstituted or optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, lower alkyl, lower alkoxy, nitro, cyano, C1-C3 perfluoro alkyl, C1-C3 perfluoro alkoxy, carboxyl, RR′N—, RR′NCO—, RCONH—, RCONR′—, RO2C—, aryl-O— and heteroaryl-O—;
• alternatively, R1 and R2 taken together form a monocyclic group or a bicyclic group, wherein the monocyclic group has 4 to 7 ring atoms, including up to 2 ring heteroatoms, and the bicyclic group has 8 to 10 ring atoms, including up to 3 ring heteroatoms, and wherein the monocyclic group and bicyclic group are unsubstituted or are optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, lower alkyl, lower alkoxy, amino, nitro, cyano, C1-C3 perfluoro alkyl, C1-C3 perfluoro alkoxy, carboxyl, aryl and heteroaryl;
• R3 is selected from H, lower alkyl, substituted lower alkyl, and RR′N—(C2-4 alkyl)-;
• R4 is selected from the group consisting of H, halo, hydroxy, lower alkyl, lower alkoxy, nitro, cyano, C1-C3 perfluoro alkyl, C1-C3 perfluoro alkoxy, carboxyl, RR′N—, RR′NCO—, RCONH—, RCONR′—, RR′N—(C2-4 alkyl)-, and RR′N—(C2-4 alkyl)-O—;
• R5 is selected from H, lower alkyl and C3-C6 cycloalkyl;
• a is 0 or 1;
• b is 0 to 2;
• and
• each R and R′ is independently selected from H, lower alkyl, and C3-C6 cycloalkyl, or alternatively, R and R′ taken together form a 5 to 6 membered heterocyclic ring.