Agents for the Treatment of Overactive Detrusor. I. Synthesis and Structure-Activity Relationships of 1, 1'-Biphenyl Derivatives

Abstract

A series of 1, 1'-biphenyl-2, 6-dicarboxylic acid diesters were synthesized and examined for their inhibitory activity on guinea-pig detrusor muscle contraction at electrical field stimulation in vitro. Among them, 6-isopropyl 2-methyl 3-hydroxy-5-methyl-2'-nitro-(1, 1'-biphenyl)-2, 6-dicarboxylate, FR75513 (8a) was one of the potent compounds (IC₅₀=3.3×10^-6 g/ml). This compound (8a) exhibited a strong inhibitory activity on detrusor contraction after intravenous administration in anesthetized rats (ID₅₀=0.04 mg/kg).