Heterocyclic inhibitors of erk1 and erk2 and their use in the treatement of cancer

A compound of formula (II),

• or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, or stereoisomer thereof, wherein:
• R1 is C6-12aryl or 5- to 10-membered heteroaryl, which is unsubstituted or substituted with 1-3 substituents selected from halogen, C1-6alkyl, CN, hydroxyC1-6alkyl, aminoC1-6alkyl, —C1-6alkyl-O—C1-6alkyl, —C1-6alkyl-NH—C1-6alkyl, —C1-6alkyl-N—(C1-6alkyl)2, —C1-6alkyl-NH—C1-6alkyl-OH, —C1-6alkyl-NH—C1-6alkyl-C3-10cycloalkyl, —C1-6alkyl-NH—C1-6alkyl-NH—C1-6alkyl, —C1-6alkyl-NH—C(O)—C1-6alkyl, —C1-6alkyl-O—C(O)—C1-6alkyl, —C1-6alkyl-NH—C0-6alkyl-(4- to 6-membered heterocyclyl), or —C1-6alkyl-NH—C0-6alkyl-(5- to 6-membered heteroaryl), wherein the C1-6alkyl, cycloalkyl, heterocyclyl, and/or heteroaryl is unsubstituted or substituted with 1-3 substituents selected from halogen, C1-6alkyl, NH2, hydroxyC1-6alkyl, or aminoC1-6alkyl;
• n is 0 to 6;
• R2 is C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, —C1-6alkyl-O—C1-6alkyl, —C1-6alkyl-NH—C1-6alkyl, —C1-6alkyl-N—(C1-6alkyl)2, —C1-6alkyl-NH—C1-6alkyl-OH, —C1-6alkyl-NH—C1-6alkyl-C3-10cycloalkyl, —C1-6alkyl-NH—C1-6alkyl-NH—C1-6alkyl, —C1-6alkyl-NH—C(O)—C1-6alkyl, —C1-6alkyl-O—C(O)—C1-6alkyl, —C1-6alkyl-NH—C0-6alkyl-(4- to 6-membered heterocyclyl), —C(O)—NH2, —C(O)—NH—C1-6alkyl, —C(O)—N(C1-6alkyl)2, or —C1-6alkyl-NH—C0-6alkyl-(5- to 6-membered heteroaryl), wherein the C1-6alkyl, heterocyclyl, or heteroaryl is unsubstituted or substituted with 1-3 substituents selected from halogen, C1-6alkyl, cycloalkyl, NH2, hydroxyC1-6alkyl, or aminoC1-6alkyl;
• and
• R8 is H or C1-6alkyl;
• alternatively, R2, R8, and the C atom that both R2 and R8 are attached join together to form a 3- to 10-membered cycloalkyl or 4- to 10-membered heterocyclyl ring, wherein the cycloalkyl or heterocyclyl is unsubstituted or substituted with 1-3 substituents selected from hydroxyl, halogen, or C1-6alkyl;
• R3 is H or C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with 1-5 halogens;
• M is a bond or NH;
• X and Y are each independently CH, C—R7, or N;
• Z is CH or N,
• R5 is H, halogen, C1-6alkyl, or O—C1-6alkyl, wherein C1-6alkyl is unsubstituted or substituted with 1-5 halogens;
• R6 is H or C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with 1-5 halogens;
• R7 is C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with 1-5 halogens;
• and
• R4 is C1-6alkyl, C3-10cycloalkyl, C4-10cycloalkenyl, —C1-6alkyl-phenyl, —C1-6alkyl-(5 to 6-membered heteroaryl), —C1-6alkyl-(4 to 6-membered heterocyclyl), 4- or 10-membered heterocyclyl, phenyl, or 5- to 10-membered heteroaryl, wherein the alkyl, cycloalkyl, cycloalkenyl, phenyl, heteroaryl, or heterocyclyl is unsubstituted or substituted with 1-3 substituents selected from halogen, CN, —C(O)—NH2, —C(O)—NH—C1-6alkyl, —C(O)—N—(C1-6alkyl)2, —O—C1-6alkyl-NH2, —O—C1-6alkyl-NH—(C1-6alkyl), —O—C1-6alkyl-N(C1-6alkyl)2, 4- to 6-membered heterocyclyl, —C(O)-(4- to 6-membered heterocyclyl), —O-phenyl, —O—C1-6alkyl-(4- to 6-membered heterocyclyl), C1-6alkyl, C2-6alkynyl, hydroxyl, C1-6alkoxyl, or hydroxyC1-6alkyl, and the heterocyclyl or heteroaryl is unsubstituted or substituted with 1-3 substituents selected from halogen, C1-6alkyl, —C(O)—C1-6alkyl, or 4- to 6-membered heterocyclyl.