Agents for the Treatment of Overactive Detrusor. II. Synthesis and Inhibitory Activity on Detrusor Contraction of 1,1'-Biphenyl-2,6-dicarboxylic Acid Diesters with an Aminoalkyl Group in the Ester Function.
作者:Kazuhiko TAKE、Kazuo OKUMURA、Koichi TAKIMOTO、Minoru OHTSUKA、Youichi SHIOKAWA
DOI:10.1248/cpb.40.899
日期:——
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-dicarboxylate
合成了一系列具有酯功能的氨基烷基的1,1'-联苯-2,6-二羧酸二酯,并在体外和体内研究了它们对逼尿肌收缩的抑制活性。在体内试验中,观察到心律不齐为副作用。在合成的那些化合物中,2-甲基6- [4-(1-甲基哌啶基)] 3-羟基-5-甲基-2'-硝基-1,1'-联苯-2,6-二羧酸酯(18)具有很强的抑制作用体内逼尿肌收缩活性(ED50 = 0.54 mg / kg iv,ED50 = 7.2mg / kg id),且与副作用的分离效果好。选择化合物18作为进一步治疗过度逼尿肌的药物进行进一步的药理评估。