NOVEL COMPOUNDS THAT ARE ERK INHIBITORS

摘要

Disclosed are the ERK inhibitors of formula (1.0), having a pyrazolopyridine base structure, and the pharmaceutically acceptable salts thereof. Also disclosed are methods of treating cancer using the compounds of formula (1.0).;

主权项

1. A compound of the formula:or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of: —OR4 and —S(O)tR5; t is 0, 1 or 2; R2 is selected from the group consisting of: R2 is selected from the group consisting of: H, (C6-C10)aryl-(C1-C3alkyl)-heterocycloalkyl-, —(C1-C6alkyl), —(C1-C6alkyl)-O—(C1-C6alkyl), —(C1-C6alkyl)-heterocycloalkyl-(C6-C10aryl), —(C1-C6alkyl)(C6-C10)aryl, —(C1-C4alkyl)heteroaryl, —(C3-C6cycloalkyl)-(C6-C10aryl), -heterocycloalkyl-(C6-C10aryl), -fused (heterocycloalkyl)(C6-C10)aryl wherein said heterocycloalkyl is a 5 to 8 membered ring (including the two atoms common with said aryl) comprising 1-3 heteroatoms selected from the group consisting of: O, S and N, and wherein the remaining atoms are carbon, -fused ((C3-C6cycloalkyl))(C6-C10)aryl, -heterocycloalkyl-C(O)O—(C1-C6alkyl)-(C6-C10)aryl, -heterocycloalkyl-(C1-C6alkyl)-heteroaryl, heterocycloalkyl, (C3-C6cycloalkyl)-(C1-C6alkyl)- and —(C3-C6cycloalkyl); and wherein said aryl (including the aryl moiety of said fused heterocycloalkylaryl, and fused cycloalkylaryl groups), heterocycloalkyl (including the heterocycloalkyl moiety of said fused heterocycloalkylaryl group), heteroaryl, and cycloalkyl (including the cycloalkyl moiety of said fused cycloalkylaryl group) moieties of said R2 groups are optionally substituted with 1-3 substituents independently selected from the group consisting of: halo, —O—(C1-C6alkyl), —OH, —CF3, —(C1-C6alkyl), —S(O)r(C1-C6alkyl) wherein r is 0, 1 or 2, —(C1-C6alkyl)-(C3-C6 cycloalkyl), —C(O)—(C1-C6alkyl)-OH, (hydroxyl substituted —(C1-C6alkyl)), —(C1-C6alkyl)(C6-C10)aryl, —(C1-C6alkyl)(halo substituted (C6-C10)aryl), —C(O)O(C1-C6alkyl), —C(O)(C1-C6alkyl), (halo substituted —(C1-C6alkyl)), —O-(halo substituted (C1-C6alkyl)), —C(O)N(C1-C6alkyl)2 wherein each alkyl is selected independently, —C(O)NH(C1-C6alkyl), —N(C1-C6alkyl)2 wherein each alkyl is independently selected, and —NH(C1-C6alkyl); and wherein said alkyl moieties of said R2 groups are optionally substituted with 1-3 substituents independently selected from the group consisting of: halo, —O—(C1-C6alkyl), —OH and —CF3, —S(O)t(C1-C6alkyl) wherein r is 0, 1 or 2, —(C3-C6cycloalkyl), (hydroxy substituted —(C3-C6cycloalkyl)), heteroaryl, -heteroaryl-(C1-C6alkyl), heterocycloalkyl, —S(O)t(C1-C6alkyl) (wherein t is 0, 1, or 2), —C(O)O(C1-C6alkyl), —O-(halo substituted —(C1-C6alkyl)), -0(C1-C6alkyl)-O—(C1-C6alkyl), —N(C1-C6alkyl)2 wherein each alkyl is independently selected, and —NH(C1-C6alkyl); R4 is selected from the group consisting of: —(C1-C6alkyl)-O—(C1-C6alkyl), —(C1-C6alkyl)(C6-C10aryl), —(C1-C6alkyl), —(C1-C6alkyl)-heteroaryl, —(C1-C6alkyl)-C(O)—N(C1-C6alkyl)2 (wherein each alkyl moiety is independently selected), —(C1-C6alkyl)-heterocycloalkyl, heterocycloalkyl, —(C1-C6alkyl)-(C3-C6cycloalkyl), —(C1-C6alkyl)-N(C1-C6alkyl)2 wherein each alkyl is independently selected, -(hydroxy substituted (C1-C6alkyl)), -heteroaryl and —(C3-C6cycloalkyl); and wherein said aryl, cycloalkyl, heteroaryl, and heterocycloalkyl moieties of said R4 groups are optionally substituted with 1-3 substitutents independently selected from the group consisting of: halo (e.g., F, Br, and Cl, and in one example F), ═O, —CN, —O(C1-C6alkyl) and —(C1-C6 alkyl); and wherein the alkyl moieties of said R4 groups are optionally substituted with 1-3 substituents independently selected from the group consisting of: —OH, halo (e.g., F, Br, and Cl, and in one example F), and —O(C1-C6alkyl); R5 is selected from the group consisting of: —(C1-C6alkyl), and —(C1-C6alkyl)-O—(C1-C6alkyl); and wherein said alkyl moieties of said R5 groups are optionally substituted with 1-3 substitutents independently selected from the group consisting of: halo, and —O(C1-C6alkyl); and R10 and R11 are each independently selected from the group consisting of: H, halo, —(C1 to C6alkyl), —(C3-C6 cycloalkyl), hydroxy substituted —(C1-C6alkyl), —(C1-C6alkyl)-O—(C1-C6alkyl), —(C1-C6alkyl)-N(C1-C6alkyl)2 wherein each alkyl is independently selected, —(C1-C6alkyl)-heterocycloalkyl, —NH2, —N(C1-C6alkyl)2 wherein each alkyl is independently selected, —NH(C1-C6alkyl), —(C1-C6alkyl)NH(C1-C6alkyl), —(C1-C6alkyl)NH2, —NHC(O)(C1-C6alkyl), —NH—(C6-C10aryl)-O(C1-C6alkyl), —C(O)OH, —CN, heteroaryl, -(heteroaryl-((C1-C6alkyl)-OH), ((C1-C6alkyl)heteroaryl), —C(O)-heterocycloalkyl, -oxoheteroaryl, —C(O)NH2, —C(O)N(C1-C6alkyl)2 wherein each alkyl is independently selected, —C(O)NH(C1-C6alkyl), —(C1-C6alkyl)-(C3-C6cycloalkyl), (hydroxy substituted —(C1-C6alkyl)-(C3-C6cycloalkyl)), —(C1-C6alkyl)-O—C(O)—(C1-C6alkyl), —C(O)—(C1-C6alkyl), —(C1-C6alkyl)-O—C(O)—NH(C1-C6alkyl), —(C1-C6alkyl)-O—C(O)—N(C1-C6alkyl)2 wherein each alkyl is independently selected, —(C1-C6alkyl)-(oxoheterocycloalkyl), —(C1-C6alkyl)-O-heterocyloalkyl, halo substituted (C1-C6alkyl), —(C1-C6alkyl)heteroaryl, —(C1-C6alkyl)-((C1-C6)alkoxy) substituted heteroaryl), —(C1-C6alkyl)-O—(C1-C6alkyl)-OH, —(C1-C6alkyl)-O—(C3-C6cycloalkyl)-OH, and —(C1-C6alkyl)-OH.