Modulators of Rho-associated protein kinase

A compound of formula (I) and pharmaceutically acceptable salts thereof:

• wherein
• A1, A2 or A3 are each independently selected from the group consisting of C—H, C—F, C—Cl, C-Me, C-Et, C-i-Pr, C-cyclopropyl, C-ethenyl, C-propenyl, C—CN, C—CF3, and N;
• B represents a 5 or 6 membered carbocyclic ring which is aromatic or unsaturated, a 5 or 6 membered heterocyclic ring which is aromatic or unsaturated, a 9 or 10 membered carbocyclic bicyclic ring system, or a 9 or 10 membered heterocyclic bicyclic ring system;
• wherein the bicyclic ring system is either aromatic or one of the rings within the bicyclic ring system is aromatic or unsaturated and the other ring is saturated;
• R1 is L-R2, wherein
• L is a bond or -L1-L2-,
• wherein L1 is selected from the group consisting of a bond, —(CRARB)1-3—, —O(CRARB)1-3—, —(CRARB)0-3O—, and —NRC(CRARB)1-3—;
• and
• L2 is selected from the group consisting of a bond, —(CRARB)1-3—, —O—, —NRD—, —C(O)NRD—, —NRDC(O)—, —C(O)O—, —OC(O)—, —C(O)—, —S(O)2NRD—, —NRDS(O)2—, —S(O)2—, —S(O)(NRD)—, —NRDC(O)NRE—, —OC(O)NRD—, and —C(O)NRDS(O)2—;
• and
• R2 is selected from the group consisting of H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl substituted with —ORF, C1-6 alkyl substituted with —NRFRG, C1-4 haloalkyl substituted with —ORF, C3-8 cycloalkyl substituted with OH, C1-4 alkyl substituted with 3 to 8 membered heterocycloalkyl, C1-4 alkyl substituted with 6 membered heteroaryl, —(CRHRI)1-3ORF, —(CRHRI)1-3NRFRG, —(CRNRO)1-3C(O)ORF, —(CRNRO)1-3C(O)NRFRG, C3-10 carbocyclic ring system, and 3 to 10 membered heterocyclic ring system;
• wherein the carbocyclic ring or heterocyclic ring system is unsubstituted or substituted with:
• ═O, —NRFRG, —C(O)RF, halo, —CN, C1-4 alkyl, C1-4 haloalkyl or C1-4 alkyl substituted with —ORF;
• R4 is independently selected at each occurrence from the group consisting of halo, C1-4 alkyl, C1-4 haloalkyl, —CN, C1-4 alkyl substituted with —ORJ, C1-4 alkyl substituted with —NRJRK, and 3 to 8 membered heterocycloalkyl;
• R5 is selected from the group consisting of H, C1-4 alkyl, C1-4 alkyl substituted with —ORF, C1-4 alkyl substituted with —NRLRL, C3-8 cycloalkyl, substituted or unsubstituted phenyl, C1-4 alkyl substituted with a 3 to 8 membered heterocycloalkyl, and substituted or unsubstituted 5 or 6 membered heteroaryl;
• wherein the phenyl or heteroaryl group may be substituted by 1 or 2 R9;
• R6 is selected from the group consisting of H and methyl;
• R8 is selected from the group consisting of H, Cl, F, CN, and Me;
• R9 is selected from the group consisting of halo and C1-4 alkyl;
• n is 0, 1, or 2;
• RA and RB are selected from the group consisting of H, C1-4 alkyl, and C1-4 haloalkyl;
• or RA and RB together with the atom to which they are attached form a 3 to 6 membered cycloalkyl ring or a 3 to 6 membered heterocycloalkyl ring;
• RC, RD, RE, RF and RG are each independently selected from the group consisting of H, C1-4 alkyl, and C1-4 haloalkyl;
• RH and RI are each H except one pair of RH and RI on the same carbon atom, together with that carbon atom, form a 3 to 6 membered cycloalkyl ring or a 3 to 6 membered heterocycloalkyl ring;
• and
• RJ, RK, RL, RM, RN and RO are each independently at each occurrence selected from the group consisting of H and C1-4 alkyl.