443330-59-4

Upstream product

• 95-54-5 1,2-diamino-benzene 
• 6160-65-2 1,1'-Thiocarbonyldiimidazole 
• 171846-13-2 trans-benzyl {4-[(tert-butoxycarbonyl)amino]cyclohexyl}methylcarbamate 
• 27687-12-3 (1r,4r)-4-({[(benzyloxy)carbonyl]amino}methyl)cyclohexane-1-carboxylic acid 

Relevant academic research and scientific papers

Design and synthesis of 1,5- and 2,5-substituted tetrahydrobenzazepinones as novel potent and selective integrin αVβ3 antagonists

The design and synthesis of novel integrin αVβ3 antagonists based on a 1,5- or 2,5-substituted tetrahydrobenzaezpinone core is described. In vitro activity of respective compounds was determined via αVβ3 binding assay, and selected derivatives were submitted to further characterization in functional cellular assays. SAR was obtained by modification of the benzazepinone core, variation of the spacer linking guanidine moiety and core, and modification of the guanidine mimetic. These efforts led to the identification of novel αVβ3 inhibitors displaying potency in the subnanomolar range, selectivity versus αIIbβ3 and functional efficacy in relevant cellular assays. A method for the preparation of enantiomerically pure derivatives was developed, and respective enantiomers evaluated in vitro. Compounds 31 and 37 were assessed for metabolic stability, resorption in the Caco-2 assay and pharmacokinetics.

Synthesis and SAR of N-substituted dibenzazepinone derivatives as novel potent and selective αVβ3 antagonists

Synthesis and SARs of new integrin αVβ3 antagonists based on an N-substituted dibenzazepinone scaffold are described. Variation of spacer and guanidine mimetic led to potent compounds exhibiting an IC50 towards αVβ3 in the nanomolar range, high selectivity versus integrin αIIbβ3 and efficacy in functional cellular assays.