Inhibitors of ERK protein kinase and uses thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Z1 is nitrogen or CRx;
• Rx is selected from R, halogen, CN, NO2, OR, SR, N(R)2, C(O)R, or CO2R, or:
• Rx and U—R1 are taken together to form an optionally substituted 5-7 membered saturated, partially unsaturated, or fully unsaturated ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Z2 is nitrogen or C-T(m)Ry;
• L is a saturated or unsaturated, straight or branched C1-6 alkylidene chain wherein:
• up to three methylene units of the chain are optionally and independently replaced by —C(R′)2, —C(O)—, —C(O)C(O)—, —C(O)NR—, —C(O)NRNR—, —CO2—, —OC(O)—, —NRCO2—, —O—, —NRC(O)NR—, —OC(O)NR—, —NRNR—, —NRC(O)—, —S—, —SO—, —SO2—, —NR—, —SO2NR—, or —NRSO2—, wherein:
• each R′ is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group;
• and
• two R′ on the same carbon atom of L are optionally taken together with said carbon atom to form a 3-7 membered ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• two R′, two R, or an R group and an R′ group, on different atoms of L are optionally taken together with said atoms to form a 3-7 membered ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• provided that L does not comprise a saturated ring directly attached to Ring A;
• T and Q are each independently selected from a saturated or unsaturated C1-6 alkylidene chain wherein:
• up to two methylene units of the chain are optionally and independently replaced by —C(O)—, —C(O)C(O)—, —C(O)NR—, —C(O)NRNR—, —CO2—, —OC(O)—, —NRCO2—, —O—, —NRC(O)NR—, —OC(O)NR—, —NRNR—, —NRC(O)—, —S—, —SO—, —SO2—, —NR—, —SO2NR—, or —NRSO2—;
• m is zero or one;
• each R is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or:
• two R on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclyl or heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Ry is selected from CN, halogen, N(R)2, OR, R, or Ar;
• each Ar is an optionally substituted ring selected from a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 3-10 membered heterocyclyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R1 is selected from CN, R, Ar, —(CH2)yCH(R3)R4, or —(CH2)yCH(R3)CH(R4)2;
• each y is independently 0-6;
• U is selected from a valence bond, —O—, —S—, —N(R)—, or a C1-6 alkylidene chain wherein up to two methylene units of U are optionally and independently replaced by —O—, —S—, —SO, —SO2—, —N(R)SO2—, —SO2N(R)—, 'N(R)—, —CO—, —CO2—, —N(R)CO—, —N(R)C(O)O—, —N(R)CON(R)—, —N(R)SO2N(R)—, —N(R)N(R)—, —C(O)N(R)—, or —OC(O)N(R)—;
• R2 is selected from (CH2)yCH(R4)2 or (CH2)yCH(R)CH(R3)CH(R4)2;
• R3 is selected from R, (CH2)wOR, (CH2)wN(R)2, or (CH2)wSR;
• each w is independently 0-4;
• and
• each R4 is independently selected from optionally substituted C1-6 aliphatic, Ar, (CH2)wOR, CO2R, (CH2)wN(R)2, N(Ar)(R), (CH2)wSR, NRC(O)R, NRC(O)N(R)2, C(O)N(R)2, SO2R, NRSO2R, C(O)R, CN, or SO2N(R)2;
• wherein,
• each optional substituent on any aryl and heteroaryl group is, independently, selected from:
• halogen, —Ro, —ORo, —SRo, 1,2-methylenedioxy, 1,2-ethylenedioxy, acyloxy, phenyl (Ph), Ph substituted with Ro, —O(Ph), O(Ph) substituted with Ro, —CH2(Ph), —CH2(Ph) substituted with Ro, —CH2CH2(Ph), —CH2CH2(Ph) substituted with Ro, —NO2, —CN, —N(Ro)2, —NRoC(O)Ro, —NRoC(O)N(Ro)2, —NRoCO2Ro, —NRoNRoC(O)Ro, —NRoNRoC(O)N(Ro)2, —NRoNRoCO2Ro, —C(O)C(O)Ro, —C(O)CH2C(O)Ro, —CO2Ro, —C(O)Ro, —C(O)N(Ro)2, —OC(O)N(Ro)2, —S(O)2Ro, —SO2N(Ro)2, —S(O)Ro, —NRoSO2N(Ro)2, —NRoSO2Ro, —C(═S)N(Ro)2, —C(═NH)—N(Ro)2, or —(CH2)yNHC(O)Ro, where y is 0-6, wherein each Ro is independently selected from hydrogen, an optionally substituted C1-6 aliphatic, an unsubstituted 5-6 membered heteroaryl or heterocyclic ring, phenyl (Ph), —O(Ph), or —CH2(Ph)—CH2(Ph). Substituents on the aliphatic group of Ro are selected from NH2, NH(C1-4 aliphatic), N(C1-4 aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo(C1-4 aliphatic)), or halo(C1-4 aliphatic);
• and
• each optional substituent on any aliphatic, haloaliphatic, cyclo-aliphatic, and heterocyclyl groups is, independently, as defined for said aryl and heteroaryl groups and additionally comprise:
• ═O, ═S, ═NNHR*, ═NN(R*)2, ═NNHC(O)R*, ═NNHCO2(alkyl), ═NNHSO2(alkyl), or ═NR*, wherein each R* is independently selected from hydrogen or an optionally substituted C1-6 aliphatic, and where optional substituents on said aliphatic group of R* are selected from NH2, NH(C1-4 aliphatic), N(C1-4 aliphatic)2, halogen, C1-4 aliphatic, OH, O(C1-4 aliphatic), NO2, CN, CO2H, CO2(C1-4 aliphatic), O(halo-C1-4 aliphatic), and halo(C1-4 aliphatic), wherein each of the foregoing C1-4 aliphatic groups of R* is unsubstituted.