194224-16-3

Upstream product

• 194224-13-0 1-Phenyl-4-trifluoromethanesulfonyloxy-isoquinoline-3-carboxylic acid ethyl ester 
• 94905-48-3 4-hydroxy-1-phenyl-isoquinoline-3-carboxylic acid ethyl ester 
• 194224-15-2 ethyl 4-methyl-1-phenylisoquinoline-3-carboxylate 

Relevant academic research and scientific papers

Mapping the peripheral benzodiazepine receptor binding site by conformationally restrained derivatives of 1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinolinecarboxamide (PK11195)

A synthetic-computational approach to the study of the binding site of peripheral benzodiazepine receptor (PBR) ligands related to 1-(2- chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195, 1) within their receptor has been developed. A wide series of conformationally restrained derivatives of 1 has been designed with the aim of probing the PBR binding site systematically. The synthesis of these compounds involves palladium-catalyzed coupling and amidation as the key steps. Twenty-nine rigid and semirigid derivatives of 1 were tested in binding studies using [3H]-1, and most of these showed PBR affinities in the nanomolar range. The essential role of the carbonyl moiety as a primary pharmacophoric element in the recognition by and the binding to PBR has been confirmed, and the restricted range of the carbonyl orientations, which characterizes the moss potent ligands, points to a specific hydrogen-bonding interaction, mainly directed by the geometrical factors, when the electronic ones are fulfilled. Moreover, the fundamental importance of the short-range dispersive interactions in the modulation of the binding affinity and, hence, in the stabilization of the ligand-receptor complex, emerged from the QSAR models reported.