Document Report Card

ID: ALA1154353

Journal: J Med Chem

Title: Stereoselective behavior of the functional diltiazem analogue 1-[(4-chlorophenyl)sulfonyl]-2-(2-thienyl)pyrrolidine, a new L-type calcium channel blocker.

Authors: Carosati E, Budriesi R, Ioan P, Cruciani G, Fusi F, Frosini M, Saponara S, Gasparrini F, Ciogli A, Villani C, Stephens PJ, Devlin FJ, Spinelli D, Chiarini A.

Abstract: We studied the stereoselective behavior of 1-[(4-chlorophenyl)sulfonyl]-2-(2-thienyl)pyrrolidine, a recently described blocker of cardiovascular L-type calcium channels that binds to the diltiazem site. Given the stereocenter at C-2 of the pyrrolidine ring, the two enantiomers were separated by chiral HPLC and, using VCD in conjunction with DFT calculations of chiroptical properties, the absolute configuration was assigned as R-(+)/S-(-). For both forms, functional, electrophysiological, and binding properties were studied and the three-dimensional superimpositions of the two enantiomers over diltiazem were obtained in silico. The significant differences observed for the two enantiomers well agreed with the experimental data, and molecular regions were hypothesized as responsible for the cardiac stereoselectivity and vascular stereospecificity.

CiteXplore: 19831392

DOI: 10.1021/jm9008696