Chemical and Pharmaceutical Bulletin p. 899 - 906 (1992)
Update date:2022-09-26
Topics:
Take
Okumura
Takimoto
Ohtsuka
Shiokawa
A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicahboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2 mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.
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