| 主权项 |
1. A method of inhibiting an activity of a JAK kinase, comprising contacting the JAK kinase with an amount of a compound effective to inhibit an activity of the JAK kinase, wherein the compound is a compound of formula Ior pharmaceutically acceptable salt thereof, wherein:
ring A is heteroaryl; p is 0, 1, 2 or 3 when ring A is monocyclic or p is 0, 1, 2, 3, 4, or 5 when ring A is bi- or tricyclic; q is 0, 1, 2 or 3; X is selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, carboxyl, carboxyl ester, cyano, halo, nitro, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkynyl, substituted cycloalkynyl; Y is selected from the group consisting of hydrogen, alk1-SO2N(R4)R5 and alk1-N(R4)SO2R5; W is selected from the group consisting of alk2-SO2N(R6)R7 and alk2-N(R6)SO2R7; alk1 and alk2 are each independently a bond, straight or branched chain C1-6 alkylene group, cycloalkylene or substituted cycloalkylene wherein:
if W is alk2-SO2N(R6)R7 and alk2 is a bond, then Y is alk1-N(R4)SO2R5 and alk1 is a bond; R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl and substituted cycloalkyl; each R2 independently is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkynyl, alkynyloxy, amino, substituted amino, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, cycloalkyl, substituted cycloalkyl, cycloalkoxy, substituted cycloalkoxy, heteroaryl, substituted heteroaryl, heteroaryloxy, substituted heteroaryloxy, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted heterocyclyloxy, aminoacyl, aminoacyloxy, carboxyl, carboxyl ester, carbonate ester, nitro, halo and oxo;
wherein if R2 is oxo, then the oxo substituent is attached to a nonaromatic portion of ring A; or R4 and one of R2 together with the intervening atoms bound thereto form a heterocyclic or a substituted heterocyclic fused to ring A; or
R5 and one of R2 together with the intervening atoms bound thereto form a heterocyclic or a substituted heterocyclic fused to ring A; Z1, Z2, and Z3 each independently is carbon or nitrogen, wherein 0 or 1 of Z1, Z2, and Z3 is N; and
W is not attached to Z1, Z2 or Z3 when said Z1, Z2 or Z3 is nitrogen; each R3 independently is selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkynyl, alkynyloxy, amino, substituted amino, aryl, substituted aryl, aryloxy, substituted aryloxy, cyano, cycloalkyl, substituted cycloalkyl, cycloalkoxy, substituted cycloalkoxy, heteroaryl, substituted heteroaryl, heteroaryloxy, substituted heteroaryloxy, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted heterocyclyloxy, aminoacyl, aminoacyloxy, carboxyl, carboxyl ester, carbonate ester, nitro, halo, and aminosulfonyl; or
R6 and one of R3, together with the intervening atoms bound thereto form a heterocyclic or a substituted heterocyclic fused to the ring containing Z1, Z2 and Z3; orR7 and one of R3, together with the intervening atoms bound thereto form a heterocyclic or a substituted heterocyclic fused to the ring containing Z1, Z2 and Z3; or R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl and M+, wherein M+is a counterion selected from the group consisting of K+, Na+, Li+and +N(R8)4, wherein R8 is hydrogen or alkyl, and the nitrogen of —SO2N(R4)R5 or —N(R4)SO2R5 is N−; or
R4 and R5 together with the intervening atom or atoms bound thereto form a heterocyclic or substituted heterocyclic group; or R5 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, amino, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and acyl; or
R4 and R5 together with the intervening atom or atoms bound thereto form a heterocyclic or a substituted heterocyclic group; R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, carboxyl, carboxyl ester, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl and M+, wherein M+is a counterion selected from the group consisting of K+, Na+, Li+or +N(R8)4, wherein R8 is hydrogen or alkyl, and the nitrogen of —SO2N(R6)R7 or —N(R6)SO2R7 is N−; or
R6 and R7 together with the intervening atom or atoms bound thereto, form a heterocyclic or a substituted heterocyclic group; orif W is alk2-SO2N(R6)R7, then R6 and R7 together with the nitrogen atom bound thereto optionally form —N═C(OR9)2 wherein each R9 independently is an alkyl group; and R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, amino, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carboxyl, carboxyl ester, and acyl; provided that when X is hydrogen, ring A is not benzimidazolyl or indazolyl. |
