In Vitro and In Vivo Characterization of Alpha-1A Selective Agonists and Their Utility for Stress Incontience

Medicinal Chemistry Research
2004.0

Abstract

SAR studies were conducted around a series of arylalkylimidazoles and arylalkylimidazolines based upon the core structure of A-61603. Changes in ring size, the heterocyclic appendage, aromatic substitution and absolute stereochemistry were examined. Compounds were evaluated for subtype selectivity in vitro using radioligand binding and functional tissue strip assays. In vivo, selectivity for effects on intraurethral pressure (IUP) versus mean arterial pressure (MAP) was determined in anesthetized dogs. Compounds were identified that displayed selectivity in vitro for the α₁ₐ subtype and that also showed enhanced urethral selectivity relative to non-subtype selective agents.

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