The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.
Journal Article (Journal Article)
Rac-ML-1035 (MDL 201,035: 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide hydrochloride) is a racemic gastroprokinetic with serotonergic (5-hydroxytryptamine, 5-HT) activity and a novel chiral sulfoxide substituent. Chromatographic and chemical methods have been developed to resolve the enantiomers of rac-ML-1035, and the absolute configuration of the (R)-enantiomer has been determined. We also report pharmacological characterization of rac-ML-1035 and its respective isomers. Radioligand binding to rat cortical membranes revealed that (R)-ML-1035 (MDL 201,226) and (S)-ML-1035 (MDL 201,227) had equivalent activity at the 5-HT3 receptor. However, in isolated tissue studies including field-stimulated guinea pig ileum, field-stimulated rat fundic strip, and nonstimulated guinea pig ileum, (S)-ML-1035 was equally potent yet had greater maximal activity than (R)-ML-1035 in eliciting or facilitating cholinergic contractions. Thus, enantiomers of rac-ML-1035 can be resolved, and the relative configuration of these isomers influences their pharmacological activity.
Full Text
Duke Authors
Cited Authors
- Butler, BT; Silvey, G; Houston, DM; Borcherding, DR; Vaughn, VL; McPhail, AT; Radzik, DM; Wynberg, H; ten Hoeve, W; van Echten, E
Published Date
- January 1992
Published In
Volume / Issue
- 4 / 3
Start / End Page
- 155 - 162
PubMed ID
- 1586586
Electronic International Standard Serial Number (EISSN)
- 1520-636X
International Standard Serial Number (ISSN)
- 0899-0042
Digital Object Identifier (DOI)
- 10.1002/chir.530040305
Language
- eng