4-Aryl-3-(mercapto)quinolin-2-ones: novel maxi-K channel opening relaxants of corporal smooth muscle

Piyasena Hewawasam; Wenhong Fan; Deborah A Cook; Kimberly S Newberry; Christopher G Boissard; Valentin K Gribkoff; John Starrett; Nicholas J Lodge

doi:10.1016/j.bmcl.2004.06.051

4-Aryl-3-(mercapto)quinolin-2-ones: novel maxi-K channel opening relaxants of corporal smooth muscle

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4479-82. doi: 10.1016/j.bmcl.2004.06.051.

Authors

Piyasena Hewawasam¹, Wenhong Fan, Deborah A Cook, Kimberly S Newberry, Christopher G Boissard, Valentin K Gribkoff, John Starrett, Nicholas J Lodge

Affiliation

¹ Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]

PMID: 15357975
DOI: 10.1016/j.bmcl.2004.06.051

Abstract

A novel series of 4-aryl-3-(mercapto)quinolin-2-one derivatives was prepared and evaluated as openers of the cloned maxi-K channel hSlo expressed in Xenopus laevis oocytes by utilizing electrophysiological methods. The effect of these maxi-K openers on corporal smooth muscle was studied in vitro using isolated rabbit corpus cavernosum. In vivo efficacy has been demonstrated with a selective maxi-K opening relaxant in a rat model of erectile function.

Publication types

Comparative Study

MeSH terms

Animals
Female
In Vitro Techniques
Large-Conductance Calcium-Activated Potassium Channels
Male
Muscle, Smooth, Vascular / drug effects*
Muscle, Smooth, Vascular / physiology
Penis / drug effects*
Penis / physiology
Potassium Channels, Calcium-Activated / physiology*
Quinolones / chemistry*
Quinolones / pharmacology
Rabbits
Rats
Rats, Inbred F344
Vasodilation / drug effects*
Vasodilation / physiology
Xenopus laevis

Substances

Large-Conductance Calcium-Activated Potassium Channels
Potassium Channels, Calcium-Activated
Quinolones