Pyrazole-derived kinase inhibitors and uses thereof

A compound of formula I:

• 210
• or a pharmaceutically acceptable derivative thereof, wherein
• B is a phenyl ring having a substituent -L-A and 0-3 R2 substituents;
• L is an optionally substituted C1-C6 alkylidene chain;
• wherein at least 1 and optionally up to 2 methylene units are replaced by —O—, —C(O)—, —C(O)C(O)—, —C(O)NR8—, —C(O)NR8NR8—, —CO2—, —OC(O)—, —NR8CO2—, —NR8C(O)NR8—, —OC(O)NR —, —NR8—, —NR8NR8—, —NR8CO—, —S—, —SO—, —SO2—, —SO2NR8—, —NR8SO2—, —NR8SO2NR8—, —N(R8)O—, or —ON(R8)—;
• A is
• 211
• Q is an optionally substituted C1-C6 alkylidene chain, wherein up to two methylene units are replaced by —C(O)—, —C—(O)C(O)—, —C(O)NR7—, —C(O)NR7NR7—, —CO2—, —OC(O)—, —NR7CO2—, —O—, —NR7C(O)NR7—, —OC(O)NR7—, —NR7NR7—, —NR7C(O)—, —S—, —SO—, —SO2—, —NR7—, —SO2NR7—, —NR7SO2—,
• or —NR7SO2NR7—;
• n is zero or one;
• R1 is hydrogen, R, fluoro, —CN, N(R7)2, OR7, NR7C(O)R7, NR7C(O)N(R7)2, C(O)N(R7)2, SO2R7, NR7SO2R7, or SO2N (R7)2;
• each R2 is independently selected from R, OH, OR, SH, SR, nitro, N (R7)2, halogen, CF3, or cyano;
• R3 is hydrogen, R, OH, OR, N(R7)2, fluoro, or CN;
• R4 is selected from —(CH2)yR6, —(CH2)yR10, —CH2)yCH(R6)2, —(CH2)yCH(R10)2, —(CH2)yCH(R10)CH(R6)2, —(CH2)yCH(R10)(R6), —N(R5)2, or —NR5(CH2)yN(R5)2;
• each R is independently selected from an optionally substituted group selected from C1-6 aliphatic, C6-10 aryl, heteroaryl having 5-10 ring atoms, or heterocyclyl having 3-10 ring atoms;
• each R5 is independently selected from R, —(CH2)yR6, —(CH2)yCH(R6)2, R7, —C(O)R7, —CO2R7, —C(O)N(R7)2, or —SO2R7;
• each y is independently 0-6;
• each R6 is independently selected from hydrogen, R, —(CH2)yR, —OH, —OR, —CO2R, —(CH2)yN(R7)2, —N(R7)2, —OR7, —SR7, —NR7C(O)R7, —NR7C(O)N(R7)2, —C(O)N(R7)2, —SO2R7, —NR7SO2R7, —C(O)R7, —CN, or —SO2N(R7)2;
• each R7 is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, or two R7 on the same nitrogen are taken together with the nitrogen to optionally form a 5-8 membered heterocyclic or heteroaryl ring;
• each R8 is independently selected from hydrogen, R, —(CH2)yR9, —(CH2)yCH(R9)2, —(CH2)yC(O)R9, R9, or R7;
• each R9 is independently selected from hydrogen, R, —OH, —OR, —SR, —S(O)R, —SO2R, —C(O)R6, —CO2R6, NR2, halo, cyano, or nitro;
• each R10 is independently selected from R, —(CH2)OR7, —(CH2)wN (R5)2, or —(CH2)wSR7;
• and
• each w is independently 0-4;
• provided that when Qn—R4 is
• 212
• R1 is H,
• and R3 is H, and R2 is a meta substituent Cl, then -L-A is not a para substituent
• 213
• or
• 214
• and
• when Qn—R4 is
• 215
• R1 is NH2, R2 is a meta substituent Cl, and R3 is H, then -L-A is not a para substituent
• 216