Synthesis and muscarinic properties of (1S*,3R*,5R*)-trimethyl(1-methyl-6-oxabicyclo[3.1.0]hex-3-yl)methyl ammonium iodide

Chem Pharm Bull (Tokyo). 1994 Jun;42(6):1286-90. doi: 10.1248/cpb.42.1286.

Abstract

To acquire more information about the so-called "muscarinic subsite", compound 4 was synthesized and tested. The results show that in comparison with deoxamuscarine (23) the muscarinic potency of 4 on M2 and M3 subtypes is not significantly altered by the presence of an epoxidic function, which confirms the donor-acceptor hydrogen bonding character of this receptive site. Conversely, there is a negative influence on the transduction processes. In addition, a second hydroxylic function bound on the carbon carrying the terminal methyl of the fourth substituent on the nitrogen dramatically affects the muscarinic behavior; the resulting compounds (11-14) lack any agonist or antagonist activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Parasympathomimetics / chemical synthesis*
  • Parasympathomimetics / pharmacology
  • Quaternary Ammonium Compounds / chemical synthesis*
  • Quaternary Ammonium Compounds / pharmacology
  • Receptors, Muscarinic / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Parasympathomimetics
  • Quaternary Ammonium Compounds
  • Receptors, Muscarinic
  • trimethyl(1-methyl-6-oxabicyclo(3.1.0)hex-3-yl)methylammonium