2. Academic Validation
  3. Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties

Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties

  • J Med Chem. 1997 Jan 31;40(3):385-90. doi: 10.1021/jm960233u.
N H Lin 1,  D E Gunn,  K B Ryther,  D S Garvey,  D L Donnelly-Roberts,  M W Decker,  J D Brioni,  M J Buckley,  A D Rodrigues,  K G Marsh,  D J Anderson,  J J Buccafusco,  M A Prendergast,  J P Sullivan,  M Williams,  S P Arneric,  M W Holladay
Affiliations

Affiliation

  • 1 Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
PMID: 9022806 DOI: 10.1021/jm960233u
Abstract

2-Methyl-3-(2(S)-pyrrolidinylmethoxy)pyridine, ABT-089 (S-4), a member of the 3-pyridyl ether class of nicotinic acetylcholine receptor (nAChR) ligands, shows positive effects in rodent and primate models of cognitive enhancement and a rodent model of anxiolytic activity and possesses a reduced propensity to activate peripheral ganglionic type receptors. The profiles of S-4, its N-methyl analogue, and the corresponding enantiomers across several measures of cholinergic channel function in vitro and in vivo are presented, together with in vitro metabolism and in vivo bioavailability data. On the basis of its biological activities and favorable oral bioavailability, S-4 is an attractive candidate for further evaluation as a treatment for cognitive disorders.

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