Modulators of C3a receptors

摘要

Heterocyclic compounds that modulate C3a receptors and their use in the treatment or prevention of inflammatory diseases, infectious diseases, cancers, metabolic disorders, obesity, type 2 diabetes, metabolic syndrome and associated cardiovascular diseases are described. The use of the compounds in stimulating or suppressing an immune response is also described together with pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts.

主权项

1. A compound of formula (I): wherein the ring A is selected from one of the following: wherein X is N or CH;
Y is O, S, NH, N(C1-3alkyl) or CH2; andZ is N or C, provided that when Z is N, R3 is absent; wherein X is O, S, NH, N(C1-3alkyl) or CH2;
Y is N; andZ is N or C, provided that when Z is N, R3 is absent; wherein X is N or CH;
Y is N or CH; andZ is O, S, N or CH, provided that when Z is O or S, R3 is absent; R1 is selected from arginine or arginine mimetics; R3 is selected from hydrogen, halogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl; R4 is selected from alkyl, alkenyl, —(CH2)mcycloalkyl, —(CH2)maryl, —(CH)mheterocyclyl, —(CH2)mheteroaryl, —(CH2)mNHC(═NH)NH2, —(CH2)mCONH2, —(CH2)mCO2H, —(CH2)mSR6, —(CH2)mOR6, R5 is selected from alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl, heteroaryl or —NHR7, R6 is selected from hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl; R7 is selected from —C(O)R8, —C(O)OR8, —C(O)NHR8 or —S(O)2R8; R8 is selected from alkyl, alkenyl, —(CHR9)pcycloalkyl, —(CHR9)pcycloalkenyl, —(CHR9)paryl, —(CHR9)pheterocyclyl or —(CHR9)pheteroaryl; R9 is selected from hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl; m is 0 or an integer from 1 to 6; and p is 0 or an integer from 1 to 6; wherein each cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocyclyl group may be optionally substituted with one or more optional substituents; or a pharmaceutically acceptable salt thereof.