Compostions useful as inhibitors of JAK and other protein kinases

A compound of formula I:

• 227
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is Q-Ar1,
• wherein Q is a bond or is a C1-2 alkylidene chain wherein one methylene unit of Q is optionally replaced by O, NR, NRCO, NRCONR, NRCO2, CO, CO2, CONR, OCONR, SO2, SO2NR, NRSO2, NRSO2NR, COCO, or COCH2CO;
• Ar1 is a 5-7 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein Ar1 is optionally substituted with q independent occurrences of Z-RZ;
• wherein q is 0-5, Z is a bond or is a C1-C6 alkylidene chain wherein up to two methylene units of Z are optionally and independently replaced by CO, CO2, COCO, CONR, OCONR, NRNR, NRNRCO, NRCO, NRCO2, NRCONR, SO, SO2, NRSO2, SO2NR, NRSO2NR, O, S, or NR;
• and each occurrence of RZ is independently selected from R′, halogen, NO2, CN, OR′, SR′, N(R′)2, NR′COR′, NR′CON(R′)2, NR′CO2R′, COR′, CO2R′, OCOR′, CON(R′)2, OCON(R′)2, SOR′, SO2R′, SO2N(R′)2, NR′SO2R′, NR′SO2N(R′)2, COCOR′, or COCH2COR′;
• each occurrence of R is independently hydrogen or an optionally substituted C1-6 aliphatic group;
• and each occurrence of R′is independently hydrogen or an optionally substituted C1-6 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or R and R′, two occurrences of R, or two occurrences of R′, are taken together with the atom(s) to which they are bound to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Z1 is N or CH;
• Z7 is N or C—URY;
• T and U are each independently a bond or a saturated or unsaturated C1-6 alkylidene chain, wherein up to two methylene units of the chain are optionally and independently replaced by CO, CO2, COCO, CONR, OCONR, NRNR, NRNRCO, NRCO, NRCO2, NRCONR, SO, SO2, NRSO2, SO2NR, NRSO2NR, O, S, or NR;
• RX and RY are each independently halogen, CN, NO2, or R′;
• Z2, Z5 and Z6 are each independently N or CH, provided that no more than two of Z2, Z5, and Z6 are N;
• Z3 is CR3;
• Z4 is CR4;
• wherein one of R3 or R4 is RU, and the other of R3 or R4 is RV1, wherein:
• RU is (CH2)tCN, (CH2)tNO2, (CH2)tN(R)2, (CH2)tNRC(O)R, (CH2)tCON(R)2, (CH2)tCOOR, (CH2)tSO2N(R)2, (CH2)tNRSO2R, (CH2)tNRCON(R)2, (CH2)tNRSO2N(R)2, (CH2)tCOCOR, (CH2)tAr2, wherein t is 0, 1, or 2, and Ar2 is an optionally substituted 5-7 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and RV1 is OR′.