Rigidified acetylcholine mimics: conformational requirements for binding to neuronal nicotinic receptors.
Basic Information
ID: ALA1136338
Journal: Bioorg Med Chem Lett
Title: Rigidified acetylcholine mimics: conformational requirements for binding to neuronal nicotinic receptors.
Authors: Villeneuve G, Cécyre D, Lejeune H, Drouin M, Lan R, Quirion R.
Abstract: Rigidified derivatives have been designed and synthesized assuming the g+t conformer of acetylcholine (N-C-C-O=+60 degrees, C-C-O-C=180 degrees ) as active conformation for binding to cytisine sensitive neuronal nicotinic receptors. The SAR of the compounds evaluated, along with those of more flexible analogues, support the g+t conformer hypothesis and highlight the stringent steric limitation of this nicotinic receptor sub-type. Compound 3e has low microM affinity for cytisine sensitive nicotinic receptor binding sites while being selective with regard to the alpha-bungarotoxin sensitive subclass. We also report few compounds with microM affinity for the alpha-bungarotoxin sensitive subclass.
CiteXplore: 14552793
DOI: 10.1016/s0960-894x(03)00728-5
Patent ID: ┄