Document Report Card

ID: ALA1148325

Journal: J Med Chem

Title: Synthesis and structure-activity relationships of a novel series of tricyclic dihydropyridine-based KATP openers that potently inhibit bladder contractions in vitro.

Authors: Carroll WA, Agrios KA, Altenbach RJ, Buckner SA, Chen Y, Coghlan MJ, Daza AV, Drizin I, Gopalakrishnan M, Henry RF, Kort ME, Kym PR, Milicic I, Smith JC, Tang R, Turner SC, Whiteaker KL, Zhang H, Sullivan JP.

Abstract: Structure-activity relationships were investigated on a novel series of tricyclic dihydropyridine-containing K(ATP) openers. This diverse group of analogues, comprising a variety of heterocyclic rings fused to the dihydropyridine nucleus, was designed to determine the influence on activity of hydrogen-bond-donating and -accepting groups and their stereochemical disposition. Compounds were evaluated for K(ATP) activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a subset of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation.

CiteXplore: 15163197

DOI: 10.1021/jm030357o