Scholars@Duke publication: The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.

The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.

Publication , Journal Article

Butler, BT; Silvey, G; Houston, DM; Borcherding, DR; Vaughn, VL; McPhail, AT; Radzik, DM; Wynberg, H; ten Hoeve, W; van Echten, E

Published in: Chirality

January 1992

Published version (DOI)

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.

Duke Scholars

Author Andrew T. McPhail Chemistry

Published In

Chirality

DOI

10.1002/chir.530040305

EISSN

1520-636X

ISSN

0899-0042

Publication Date

January 1992

Volume

Issue

Start / End Page

155 / 162

Related Subject Headings

X-Ray Diffraction
Stereoisomerism
Receptors, Serotonin
Rats
Organic Chemistry
Muscle Contraction
Metoclopramide
Male
In Vitro Techniques
Ileum

Citation

APA

Chicago

ICMJE

MLA

NLM

Butler, B. T., Silvey, G., Houston, D. M., Borcherding, D. R., Vaughn, V. L., McPhail, A. T., … van Echten, E. (1992). The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide. Chirality, 4(3), 155–162. https://doi.org/10.1002/chir.530040305

Butler, B. T., G. Silvey, D. M. Houston, D. R. Borcherding, V. L. Vaughn, A. T. McPhail, D. M. Radzik, H. Wynberg, W. ten Hoeve, and E. van Echten. “The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.” Chirality 4, no. 3 (January 1992): 155–62. https://doi.org/10.1002/chir.530040305.

Butler BT, Silvey G, Houston DM, Borcherding DR, Vaughn VL, McPhail AT, et al. The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide. Chirality. 1992 Jan;4(3):155–62.

Butler, B. T., et al. “The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide.” Chirality, vol. 4, no. 3, Jan. 1992, pp. 155–62. Epmc, doi:10.1002/chir.530040305.

Butler BT, Silvey G, Houston DM, Borcherding DR, Vaughn VL, McPhail AT, Radzik DM, Wynberg H, ten Hoeve W, van Echten E. The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide. Chirality. 1992 Jan;4(3):155–162.

Published In

Chirality

DOI

10.1002/chir.530040305

EISSN

1520-636X

ISSN

0899-0042

Publication Date

January 1992

Volume

Issue

Start / End Page

155 / 162

Related Subject Headings

X-Ray Diffraction
Stereoisomerism
Receptors, Serotonin
Rats
Organic Chemistry
Muscle Contraction
Metoclopramide
Male
In Vitro Techniques
Ileum