Isoxazole compositions useful as inhibitors of ERK

A compound of formula I:

• 173
• or a pharmaceutically acceptable derivative or prodrug thereof, wherein:
• Ht is a heteroaryl ring selected from pyrrol-3-yl, pyrazol-3-yl, [1,2,4]triazol-3-yl, [1,2,3]triazol-4-yl, or tetrazol-5-yl;
• said pyrrol-3-yl and pyrazol-3-yl each having R3 and QR4 substituents, and said triazole substituted by either R3 or QR4;
• A—B is N—O or O—N;
• R1 is selected from R5, fluorine, N(R5)2, OR, NRCOR, CON(R5)2, SO2R, NRSO2R, or SO2N(R5)2;
• T and Q are each independently selected from a valence bond or a linker group;
• each R is independently selected from hydrogen or an optionally substituted aliphatic group having one to six carbons;
• R2 is selected from hydrogen, CN, fluorine, or an optionally substituted group selected from aryl, heteroaryl, heterocyclyl, an acyclic aliphatic group having one to six carbons, or a cyclic aliphatic group having four to ten carbons;
• wherein R has up to one L-W substituent and up to three R8 substituents;
• L is a C1-6 alkylidene chain which is optionally substituted, and wherein up to two methylene units of L are optionally replaced by —C(O)—, —C(O)C(O)—, —CONH—, —CONHNH—, —CO2—, —OC(O)—, —NHCO2—, —O—, —NHCONH—, —OC(O)NH—, —NHNH—, —NHCO—, —S—, —SO—, —SO2—, —NH—, —SO2NH—, —NHSO2NH—, or —NHSO2—;
• W is selected from R9, CH(R9)2, CH(R9)N(R9)2, or N(R9)2;
• R3 is selected from R, OH, OR, N(R)2, fluorine, or CN;
• R4 is selected from —R6, —NH2, —NHR6, —N(R6)2, or —NR6(CH2)yN(R6)2;
• each R5 is independently selected from hydrogen or an optionally substituted aliphatic group having one to six carbons or two R5 on the same nitrogen may be taken together with the nitrogen to form a four to eight membered ring having one to three heteroatoms;
• each R6 is independently selected from R5, —(CH2)yCH(R7)2, or —(CH2)yR7;
• y is 0-6;
• each R7 is an optionally substituted group independently selected from R, aryl, aralkyl, aralkoxy, heteroaryl, heteroarylalkyl, heteroarylalkoxy, heterocyclyl, heterocyclylalkyl, heterocyclylalkoxy, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, or alkoxycarbonyl;
• each R8 is independently selected from halogen, —R′, —OR′, —SR′, —NO2, —CN, —N(R5)2, —NRC(O)R′, —NRC(O)N(R5)2, —NRCO2R′, —NRNRC(O)R′, —NRNRC(O)N(R5)2, —NRNRCO2R′, —C(O)C(O)R′, —C(O)CH2C(O)R′, —CO2R′, —C(O)R′, —C(O)N(R5)2, —OC(O)N(R5)2, —S(O)2R′, —SO2N(R5)2, —S(O)R′, —NRSO2N(R5)2, —NRSO2R′, —C(═S)N(R5)2, or —C(═NH)N(R5)2;
• wherein each R′ is independently selected from hydrogen, or an optionally substituted group selected from aliphatic, heteroaryl, heterocyclyl, or phenyl;
• and
• each R9 is independently selected from R5, R8, or an optionally substituted group selected from aryl, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl;
• provided that when Ht is a pyrazole ring, R1 is methyl in the 5-position, and T—R2 is H in the 4-position, then Ht is other than 3-ethoxycarbonylpyrazol-5-yl;
• when R1, R3 and Q—R4 are all H, then T—R2 is other than phenyl;
• and when R3 is methyl in the 5 position, Q—R4 is other than C(O)OMe in the 4 position.