Substituted 1,4-benzodiazepines and uses thereof

摘要

The present invention is directed to novel 1,4-benzodiazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I: or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: X and Y are independently -C(O)-, -CH₂- or -C(S)-; R¹, R², R³, R⁴, R⁷, R⁸, R^b, R^c, R^d and M arm defined herein; R⁵ is hydrogen, alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R⁶ is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R⁹ is cycloalkyl: aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkyl(alkyl), aralkyl or heteroarylalkyl, each of which is optionally substituted; and R¹⁰ is -(CH₂)_n-CO₂R^b, -(CH₂)_m-CO₂M, -(CH₂)_i-OH or -(CH₂)_j-CONR^cR^d n is 0-8, m is 0-8, i is 1-8 and j is 0-8.