Synthesis and biological evaluation of pyridine-modified analogues of 3-(2-aminoethoxy)pyridine as novel nicotinic receptor ligands

Nan-Horng Lin; Liming Dong; William H Bunnelle; David J Anderson; Michael D Meyer

doi:10.1016/s0960-894x(02)00740-0

Synthesis and biological evaluation of pyridine-modified analogues of 3-(2-aminoethoxy)pyridine as novel nicotinic receptor ligands

Bioorg Med Chem Lett. 2002 Nov 18;12(22):3321-4. doi: 10.1016/s0960-894x(02)00740-0.

Authors

Nan-Horng Lin¹, Liming Dong, William H Bunnelle, David J Anderson, Michael D Meyer

Affiliation

¹ Neurological and Urological Diseases Research, D-47W, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. [email protected]

PMID: 12392742
DOI: 10.1016/s0960-894x(02)00740-0

Abstract

Analogues of the potent nicotinic receptor agonist 3-(2-aminoethoxy)pyridine substituted at the 5' and 6'-positions of the pyridine ring were synthesized and tested in vitro for nicotinic receptor binding activity (displacement of [(3)H](-)cytisine from whole rat brain synaptic membranes). The substituted analogues exhibited K(i) values ranging from 0.076 to 319 nM compared to a K(i) value of 26 nM for compound 1. Among the compounds tested, 5'-vinyl-6'-chloro substituted 1 was the most potent.

MeSH terms

Animals
Brain / ultrastructure
Ligands
Nicotinic Agonists / chemical synthesis*
Nicotinic Agonists / pharmacology
Pyridines / chemical synthesis*
Pyridines / pharmacology
Pyrrolidines / pharmacology
Radioligand Assay
Rats
Receptors, Nicotinic / chemistry*
Receptors, Nicotinic / metabolism
Structure-Activity Relationship
Synaptic Membranes / metabolism

Substances

3-(2-(pyrrolidinyl)methoxy)pyridine
3-(2-aminoethoxy)pyridine
Ligands
Nicotinic Agonists
Pyridines
Pyrrolidines
Receptors, Nicotinic