Synthesis and structure-activity relationship of novel pyridyl ethers for the nicotinic acetylcholine receptor

Authors
Lee, J Davis, CB Rivero, RA Reitz, AB Shank, RP
Citation
J. Lee et al., Synthesis and structure-activity relationship of novel pyridyl ethers for the nicotinic acetylcholine receptor, BIOORG MED, 10(10), 2000, pp. 1063-1066
Citations number
20
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
10
Year of publication
2000
Pages
1063 - 1066
Database
ISI
SICI code
0960-894X(20000515)10:10<1063:SASRON>2.0.ZU;2-1
Abstract
The preparation of novel pyridyl ethers as ligands for the nicotinic acetyl choline receptor (nAChR) is described. Variations of the ring size of the a zacycle and substitution on the pyridine had dramatic effects on receptor b inding affinity with IC(50)s at the alpha(4)beta(2) nAChR ranging from 22 t o > 10,000 nM. The most potent molecule was (R)-2-chloro-3-(4-cyanophenyl)- 5-((3-pyrrolidinyl)oxy)pyridine 27f with an IC50 of 22 nM. (C) 2000 Elsevie r Science Ltd. All rights reserved.