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: ##STR00001## or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein: X and Y are independently --C(O)--, --CH.sub.2-- or --C(S)--; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.7, R.sup.8, R.sup.b, R.sup.c, R.sup.d and M are defined herein; R.sup.5 is hydrogen, alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, carboxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonylalkyl, alkylaminocarbonyl or alkylaminocarbonylalkyl; R.sup.6 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; R.sup.9 is cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkyl(alkyl), aralkyl or heteroarylalkyl, each of which is optionally substituted; and R.sup.10 is --(CH.sub.2).sub.n--CO.sub.2R.sup.b, --(CH.sub.2).sub.m--CO.sub.2M, --(CH.sub.2).sub.i--OH or --(CH.sub.2).sub.j--CONR.sup.cR.sup.d n is 0 8, m is 0 8, i is 1 8 and j is 0 8.