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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

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

Published In

Chirality

DOI

EISSN

1520-636X

ISSN

0899-0042

Publication Date

January 1992

Volume

4

Issue

3

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

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Chicago
ICMJE
MLA
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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.
Journal cover image

Published In

Chirality

DOI

EISSN

1520-636X

ISSN

0899-0042

Publication Date

January 1992

Volume

4

Issue

3

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