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

Chem Pharm Bull (Tokyo). 1992 Apr;40(4):899-906. doi: 10.1248/cpb.40.899.

Abstract

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 (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/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.

MeSH terms

  • Animals
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / pharmacology*
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / pharmacology*
  • Esters / chemical synthesis
  • Esters / pharmacology*
  • Muscle Contraction / drug effects*
  • Rats
  • Structure-Activity Relationship
  • Urination Disorders / drug therapy*

Substances

  • Biphenyl Compounds
  • Carboxylic Acids
  • Esters