Carbamoylcholine Analogs as Nicotinic Acetylcholine Receptor Agonists--Structural Modifications of 3-(dimethylamino)butyl Dimethylcarbamate (DMABC)

Bioorg Med Chem Lett. 2009 Jan 1;19(1):87-91. doi: 10.1016/j.bmcl.2008.11.011. Epub 2008 Nov 7.

Abstract

Compounds based on the 3-(dimethylamino)butyl dimethylcarbamate (DMABC) scaffold were synthesized and pharmacologically characterized at the alpha(4)beta(2), alpha(3)beta(4,) alpha(4)beta(4) and alpha(7) neuronal nicotinic acetylcholine receptors (nAChRs). The carbamate functionality and a small hydrophobic substituent in the C-3 position were found to be vital for the binding affinity to the nAChRs, whereas the carbamate nitrogen substituents were important for nAChR subtype selectivity. Finally, the compounds were found to be agonists at the alpha(3)beta(4) nAChR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbachol / analogs & derivatives*
  • Carbachol / chemical synthesis
  • Carbachol / pharmacology*
  • Carbamates / chemistry*
  • Humans
  • Nicotinic Agonists / chemical synthesis*
  • Protein Binding
  • Receptors, Nicotinic / drug effects*
  • Structure-Activity Relationship

Substances

  • Carbamates
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Carbachol