Muscarinic thioligands with cyclopentane nucleus

Bioorg Med Chem. 1996 Dec;4(12):2193-9. doi: 10.1016/s0968-0896(96)00231-3.

Abstract

Some thio- and the benzoyl-derivatives of deoxamuscarine were synthesized and tested as muscarinic agonists using radioligand binding assays and functional tests. In comparison with deoxamuscarine, used as reference compound, no dimension/distance modification is tolerated for correct lipophilic pocket recognition. The substitution of the ammonium group with a sulphonium group significantly decreased muscarinic potency. The so-called 'muscarinic sub-site' accepts relatively bulky functions as long as it is bound to the cyclopentane carrier by an oxygen bridge. Esterification of this moiety increases the M2 subtype selectivity, while etherification heightens that of M3.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cyclopentanes / chemistry*
  • Cyclopentanes / metabolism
  • Cyclopentanes / pharmacology*
  • Guinea Pigs
  • Heart / drug effects
  • Ileum / drug effects
  • Ileum / metabolism
  • Ligands
  • Male
  • Muscarine / chemistry*
  • Muscarine / metabolism
  • Muscarine / pharmacology*
  • Myocardium / metabolism
  • N-Methylscopolamine
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Parasympatholytics / pharmacology
  • Quaternary Ammonium Compounds / chemistry*
  • Quaternary Ammonium Compounds / metabolism
  • Quaternary Ammonium Compounds / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • Scopolamine Derivatives / pharmacology
  • Structure-Activity Relationship
  • Submandibular Gland / drug effects
  • Submandibular Gland / metabolism

Substances

  • 3-hydroxy-4-methyl-1-methylsulfanylmethylcyclopentane methioidide
  • 3-hydroxy-4-methylsulfanyl-1-N,N-dimethylaminomethylcyclopentane methiodide
  • Cyclopentanes
  • Ligands
  • Parasympatholytics
  • Quaternary Ammonium Compounds
  • Receptors, Muscarinic
  • Scopolamine Derivatives
  • Muscarine
  • N-Methylscopolamine