IAP ANTAGONISTS

摘要

There are disclosed compounds of formula (I) that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.;

主权项

1. A compound of Formula (I)wherein
X is absent, —(CR10R11)m—, optionally substituted heteroaryl or optionally substituted heterocyclyl, Y and Z are independently C═O, —O—, —NR9—, —CONH—, —NHCO— or may be absent; R1 and R2 are independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted arylalkyl, optionally substituted aryl, or R1 and R2 are independently optionally substituted thioalkyl wherein the substituents attached to the S atom of the thioalkyl are optionally substituted alkyl, optionally substituted branched alkyl, optionally substituted heterocyclyl, —(CH2)vCOR20, —CH2CHR21COR22 or —CH2R23; wherein
v=1-3,R29 and R22 are independently selected from OH, NR24R25 or OR26,R21 is NR24R25,R23 is optionally substituted aryl or optionally substituted heterocyclyl, where the optional substituents include alkyl and halogen,R24 is hydrogen or optionally substituted alkyl,R25 is hydrogen, optionally substituted alkyl, optionally substituted branched alkyl, optionally substituted arylalkyl, optionally substituted heterocyclyl, —CH2(OCH2CH2O)mCH3, or a polyamine chain,R26 is optionally substituted alkyl,w=1-8, where the optional substituents are OH, halogen or NH2; R3 and R4 are independently optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted arylalkoxy, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted heteroarylalkyl or optionally substituted heterocycloalkyl, wherein the substituents are alkyl, halogen or OH; R5, R6, R7 and R8 are independently hydrogen, optionally substituted alkyl or optionally substituted cycloalkyl; R9 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl or CO alkyl; R10 and R11 are independently hydrogen, halogen or optionally substituted alkyl; R12 and R13 are independently hydrogen, halogen or optionally substituted alkyl, or R12 and R13 can be taken together to form a carbocyclic ring; R14, R15, R16, R17 and R18 are independently hydrogen, halogen, optionally substituted alkyl or OR19; R19 is hydrogen, optionally substituted alkyl or optionally substituted cycloalkyl; m and n are independently 0, 1, 2, 3, or 4; o and p are independently 0, 1, 2 or 3; q is 0, 1, 2, 3, or 4; r is 0 or 1; t is 1, 2, or 3;and/or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.