Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist.

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Lin NH, Gunn DE, Li Y, He Y, Bai H, Ryther KB, Kuntzweiler T, Donnelly-Roberts DL, Anderson DJ, Campbell JE, Sullivan JP, Arneric SP, Holladay MW

Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrrolidinyl)methoxy]pyridine, A-84543, a potent nicotinic acetylcholine receptor agonist.

Bioorg Med Chem Lett. 1998 Feb 3;8(3):249-54.

PubMed ID

9871663 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Nicotine	Neuronal acetylcholine receptor subunit beta-2	EC 50 (nM)	5000	N/A	N/A	Details