Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5688
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, Fabio 
Frosini, Maria
Saponara, Simona
Gasparrini, F
Ciogli, A
Villani, C
STEPHENS P., J
DEVLIN F., J
Spinelli, D.
Chiarini, A.
Issue Date: 2009
Project: None 
Journal: JOURNAL OF MEDICINAL CHEMISTRY
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.
Description: 
36491
URI: http://hdl.handle.net/20.500.12779/5688
ISSN: 0022-2623
Appears in Collections:Publications

Show full item record

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.