787633-96-9

Upstream product

• 27298-99-3 (R)-1-(4-chlorophenyl)ethylamine 
• 1121-57-9 1-isocyanocyclohexene 
• 104-88-1 4-chlorobenzaldehyde 
• 445479-86-7 2-[N-(tert-Butyloxycarbonyl)amino]-5-iodobenzoic acid 

Downstream Products

• 787633-91-4 (3S)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(propyn-1-yl)-1,4-benzodiazepine-2,5-dione 
• 787633-65-2 (3S)-3-(4-Chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(methylthio)-1,3-dihydro-1,4-benzodiazepine-2,5-dione 
• 787633-66-3 (3R)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(methylthio)-1,3-dihydro-1,4-benzodiazepine-2,5-dione 
• 787633-67-4 (3S)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(trifluoromethylthio)-1,3-dihydro-1,4-benzodiazepine-2,5-dione 
• 787633-68-5 (3R)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(trifluoromethylthio)-1,3-dihydro-1,4-benzodiazepine-2,5-dione 
• 787633-63-0 5-{(3S)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)-ethyl]-7-iodo-2,5-dioxo-2,3,4,5-tetrahydro-benzo[e][1,4]diazepin-1-yl }-pentanoic acid tert-butyl ester 
• 787633-78-7 (3S)-3-(4-chlorophenyl)-4-[(R)-1-(4-chlorophenyl)ethyl]-7-(2-methylphenyl)-1,4-benzodiazepine-2,5-dione 

Relevant academic research and scientific papers

Enantiomerically pure 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists

The 1,4-benzodiazepine-2,5-dione is a suitable template to disrupt the interaction between p53 and Hdm2. The development of an enantioselective synthesis disclosed the stereochemistry of the active enantiomer. An in vitro p53 peptide displacement assay identified active compounds. These activities were confirmed in several cell-based assays including induction of the p53 regulated gene (PIG-3) and caspase activity.

Substituted 1,4-diazepines and uses thereof

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.