The present invention is directed to novel 1,4-diazepines, 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: R1, R2, R9, R10, Ra, Rd and M are defined herein; X is a bivalent radical of: an alkane, a cycloalkane, an optionally-substituted arene, an optionally-substituted heteroarene, an optionally-substituted arylalkane or an optionally-substituted heteroarylalkane; and R3 is —CO2Rd, —CO2M, —OH, —NHRd, —SO2Rd, —NHCONHRd, optionally-substituted amidino or optionally-substituted guanidino; or R3—X— is hydrogen or an electron pair; R4 is oxygen or —NR9R10; R5 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; and R6, R7 and R8 are independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkylalkyl, aralkyl or heteroarylalkyl, each of which is optionally substituted; or R6 and R7, together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted 1 to 3 times with Ra.

Title
Substituted 1,4-diazepines and uses thereof
Application Number
11/452861
Publication Number
20060235007
Application Date
June 14, 2006
Publication Date
October 19, 2006
Inventor
Kristi Leonard
West Chester
PA, US
Joan Gushue
Conshohocken
PA, US
Juan Jose Marugan Sanchez
Downingtown
PA, US
Louis V LaFrance
West Chester
PA, US
Daniel J Parks
Downingtown
PA, US
Raul R Calvo
Royersford
PA, US
Maxwell David Cummings
Wayne
PA, US
Pierre Raboisson
Karen L Milkiewicz
Exton
PA, US
Tianbao Lu
Churchville
PA, US
Agent
Johnson & Johnson
NJ, US
Agent
Philip S Johnson
NJ, US
IPC
C07D 243/18
C07D 413/02
C07D 403/02
A61K 31/5513
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