Title of article :
Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist
Author/Authors :
Nan-Horng Lin، نويسنده , , David E. Gunn، نويسنده , , Yihong Li، نويسنده , , Yun He، نويسنده , , Hao Bai، نويسنده , , Keith B. Ryther، نويسنده , , Theresa Kuntzweiler، نويسنده , , Diana L. Donnelly-Roberts، نويسنده , , David J. Anderson، نويسنده , , Jeffrey E. Campbell، نويسنده , , James P. Sullivan، نويسنده , , Stephen P. Arneric، نويسنده , , Mark W. Holladay، نويسنده ,
Abstract :
Analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine (A-84543, 1) with 2-, 4-, 5-, and 6-substituents on the pyridine ring were synthesized. These analogs exhibited Ki values ranging from 0.15 to > 9,000 nM when tested in vitro for neuronal nicotinic acetylcholine receptor binding activity. Assessment of functional activity at subtypes of neuronal nicotinic acetylcholine receptors indicates that pyridine substitution can have a profound effect on efficacy at these subtypes, and several subtype-selective agonists and antagonists have been identified.
