Agents for the treatment of overactive detrusor. I. Synthesis and structure-activity relationships of 1,1'-biphenyl derivatives

Chem Pharm Bull (Tokyo). 1991 Nov;39(11):2915-23. doi: 10.1248/cpb.39.2915.

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 x 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).

MeSH terms

  • Animals
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle, Smooth / drug effects
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Urinary Bladder / drug effects
  • Urination Disorders / drug therapy*

Substances

  • Biphenyl Compounds
  • FR 75513