Heterocyclic nitrogen derivatives and their application in the treatment of tissue fibrosis

摘要

A compound having the formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, ** (See formula) ** wherein, Q1 and Q2 are each independently N or CH; X is N or CH; J is -O-, -C ( = S) -, - (CH2) mO-, -C ( = O) -, -C ( = O) O-, -S ( = O) 1- , - (CH2) mN (R6) -, -N (R6) -, -S ( = O) 1N (R6) -, -CH = CH-, - N (R6) C ( = O) - or - (CH2) m-; each R1 is independently -Y-R5, where each Y is independently -O-, -C ( = S) -, - (CH2) mO-, - C ( = O) -, -C ( = O ) O-, -S ( = O) 1-, - (CH2) mN (R6) -, -N (R6) -, -S ( = O) tN (R6) -, -CH = CH- , -N (R6) C ( = O) - or - (CH2) m-; each R1a is independently H, F, Cl, Br, I, cyano, hydroxy, amino, carboxy, alkyl, haloalkyl, alkoxy, alkylamino, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkoxy, hydroxyalkyl, aminoalkoxy, alkyl (-OC ( = O) -, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkoxy or cycloalkylalkyl; each of R2 and R3 is independently H, F, Cl, Br, I, cyano, hydroxy , carboxy, alkyl, haloalkyl, alkoxy, hydroxyalkoxy, hydroxyalkyl, aminoalkoxy, haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl; each R4 is independently H, hydroxy, carboxy, Cl , I, cyano, nitro, mercapto, alkyl, haloalkyl, alkoxy, alkylamino, alkylthio, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl; each R5 is independently heterobic Bridged Icyl, Bridged Bicyclyl, Fused Bicyclyl, Fused Heterobicyclyl, Aryl, Arylalkyl, Heteroaryl, Heteroarylalkyl, Heterocyclyl, Heterocyclylalkyl, Cycloalkyl, or Cycloalkylalkyl; each R6 is H; each t is independently 0, 1 or 2; each m is independently 1, 2, 3 or 4; each of n and p is independently 0, 1, 2, 3 or 4; and k is 1, 2, 3 or 4; where each of - (CH2) mO-, - (CH2) mN (R6) -, -N (R6) -, -S ( = O) tN (R6) -, -CH = CH-, - N (R6) C ( = O) -, - (CH2) m-, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, hydroxyalkoxy, hydroxyalkyl, aminoalkoxy, alkyl-OC ( = O) -, aryl, aryloxy, heteroaryloxy , haloalkoxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, cycloalkylalkyl, bridged heterobicyclyl, bridged bicyclyl, bicyclyl fused, heteroxycyclyl fused, alkylamino and alkyl are independently or optionally substituted with = O), F, Cl, Br, I, alkyl-OC ( = O) -, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cyano, nitro, amino, alkylamino, mercapto, alkylthio, aryl, aryloxy, heteroaryl, heteroaryloxy and haloalkoxy.