Inhibitors of IAP

摘要

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds having the general formula U1-M-U2 wherein M is a linking group covalently joining R2, R3, R4 or R5 of U1 to an R2, R3, R4 or R5 group of U2; U1 and U2 have the general formula (I) and G, X1, X2, R2, R3, R3′, R4, R4′ and R5, are as described herein.;

主权项

1. A compound of formula Va, VIa, VIIa, or XX,wherein
X1 and X2 are each independently O or S; R2 is cyclohexyl, phenyl, or piperidinyl; R3 is H or alkyl; R3′ is H; R4 and R4′ are independently H or alkyl; R5 is H or alkyl; G1 and G2 are each independently IVb: whereinR1 is H;R5′ is H or alkyl;R6 and R6′ are each H;A1 is a thiazole or thiadiazole optionally substituted with acylamino, or a heterocycle; wherein each heterocycle substitution is optionally substituted with alkyl;X3 is O or S; andY is CH2; and M is —C(O)NH(CH2)7NHC(O)—, —C(O)NH(CH2)11NHC(O)—, —C(O)NH—(CH2O)2—(CH2)2—NHC(O)—, —C(O)NH—CH2CH2CH2—NRy—CH2CH2CH2—NHC(O)—, —C(O)NH—CH2—CH(OH)—CH2—NHC(O)—, —C(O)NH—CH2—C(CH3)2—CH2—NHC(O)—, or —C(O)NHCH2-phenyl-CH2—NHC(O)—;
wherein Ry is methyl, acetyl, or —C(O)—(CH2)1-6-(3-(2-amino-2-carboxyethyl)-2,5-dioxopyrrolidin-1-yl); or a pharmaceutically acceptable salt thereof.