Structure-Activity Studies of Diazabicyclo[3.3.0]octane-Substituted Pyrazines and Pyridines as Potent alpha 4 beta 2 Nicotinic Acetylcholine Receptor Ligands

A series of diazabicyclo[3.3.0]octane substituted pyridines and pyrazines was synthesized and characterized at the alpha 4 beta 2 neuronal nicotinic acetylcholine receptor (nAChR). The compounds were designed to mimic the profile of ABT-089, high affinity binding ligand for the alpha 4 beta 2 nAChR,...

Full description

Saved in:
Bibliographic Details
Published inJournal of medicinal chemistry Vol. 54; no. 21; pp. 7678 - 7692
Main Authors Scanio, Marc J. C., Shi, Lei, Bunnelle, William H., Anderson, David J., Helfrich, Rosalind J., Malysz, John, Thorin-Hagene, Kirsten K., Van Handel, Ceclia E., Marsh, Kennan C., Lee, Chih-Hung, Gopalakrishnant, Murali
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 10.11.2011
Subjects
Chemistry, Medicinal
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
CHOLINERGIC CHANNEL MODULATOR
SMOKING-CESSATION
ABT-089 2-METHYL-3(2-(S)-PYRROLIDINYLMETHOXY)PYRIDINE
ANTINOCICEPTIVE PROPERTIES
SAZETIDINE-A
PHARMACOLOGICAL CHARACTERIZATION
PARTIAL AGONIST
ALLOSTERIC MODULATION
BINDING
DEFICIT/HYPERACTIVITY DISORDER
Online AccessGet full text

Cover

More Information
Summary:A series of diazabicyclo[3.3.0]octane substituted pyridines and pyrazines was synthesized and characterized at the alpha 4 beta 2 neuronal nicotinic acetylcholine receptor (nAChR). The compounds were designed to mimic the profile of ABT-089, high affinity binding ligand for the alpha 4 beta 2 nAChR, with limited agonist activity. Carboxamide derivatives of 3-(diazabicyclo[3.3.0]octane)-substituted pyridines or 2-(diazabicyclo[3.3.0]octane)-substituted pyrazines were found to have the desired binding and activity profile. The structure-activity relationship of these compounds is presented.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm201045m