Synthesis and Pharmacological Characterization of 3-[2-((3a<i>R</i>,9b<i>R</i>)-<i>cis</i>-6-Methoxy- 2,3,3a,4,5,9b-hexahydro-1<i>H</i>- benz[<i>e</i>]isoindol-2-yl)ethyl]pyrido[3‘,4‘:4,5]thieno[3,2-<i>d</i>]pyrimidine- 2,4(1<i>H</i>,3<i>H</i>)-dione (A-131701): A Uroselective α_1A Adrenoceptor Antagonist for the Symptomatic Treatment of Benign Prostatic Hyperplasia

Synthesis and Pharmacological Characterization of 3-[2-((3aR,9bR)-cis-6-Methoxy- 2,3,3a,4,5,9b-hexahydro-1H- benz[e]isoindol-2-yl)ethyl]pyrido[3‘,4‘:4,5]thieno[3,2-d]pyrimidine- 2,4(1H,3H)-dione (A-131701):  A Uroselective α1A Adrenoceptor Antagonist for the Symptomatic Treatment of Benign Prostatic Hyperplasi

Synthesis and Structure−Activity Relationships of a Novel Series of Tricyclic Dihydropyridine-Based K_ATP Openers That Potently Inhibit Bladder Contractions in Vitro

Structure−activity relationships were investigated on a novel series of tricyclic dihydropyridine-containing KATP 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 KATP 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