Dialkylaminoalkyl esters of 2,2-diphenyl-2-alkylthioacetic acids: a new class of potent and functionally selective muscarinic antagonists

Bioorg Med Chem. 1994 Oct;2(10):1061-74. doi: 10.1016/s0968-0896(00)82056-8.

Abstract

The synthesis and pharmacological activity as muscarinic antagonists of a number of 2-alkylthio-2,2-diphenylacetic acid esters are reported. The compounds studied are potent muscarinic antagonists and many of them show from moderate to high selectivity toward M2 or toward M1 and M2 receptors when tested on tissues but lack selectivity on five muscarinic human receptors (m1-m5) cloned and expressed in CHO-K1 cells. As a consequence, the compounds behave as functionally selective antagonists. Those showing M2 selectivity appear to be good drug candidates for the treatment of cognitive disorders connected with central cholinergic deficit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology
  • Diphenylacetic Acids / chemistry
  • Diphenylacetic Acids / pharmacology*
  • Esters / chemistry
  • Esters / pharmacology
  • Guinea Pigs
  • Heart / drug effects
  • Ileum / drug effects
  • Male
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / pharmacology*
  • Rabbits
  • Structure-Activity Relationship
  • Sulfoxides / chemistry
  • Sulfoxides / pharmacology
  • Vas Deferens / drug effects

Substances

  • Diphenylacetic Acids
  • Esters
  • Muscarinic Antagonists
  • Sulfoxides