Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with alpha7 selectivity

Gunter Karig; Jonathan M Large; Christopher G V Sharples; Andrew Sutherland; Timothy Gallagher; Susan Wonnacott

doi:10.1016/s0960-894x(03)00594-8

Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with alpha7 selectivity

Bioorg Med Chem Lett. 2003 Sep 1;13(17):2825-8. doi: 10.1016/s0960-894x(03)00594-8.

Authors

Gunter Karig¹, Jonathan M Large, Christopher G V Sharples, Andrew Sutherland, Timothy Gallagher, Susan Wonnacott

Affiliation

¹ School of Chemistry, University of Bristol, UK.

PMID: 14611837
DOI: 10.1016/s0960-894x(03)00594-8

Abstract

Four racemic phenyl-substituted analogues 3-6 of the potent nicotinic agonist UB-165 1 have been synthesised and evaluated against the alpha(4)beta(2), alpha(3)beta(4), and alpha(7) neuronal nicotinic receptors. The 2'-phenyl derivative 3 shows no activity at these major receptor subtypes, while the 4'-phenyl analogue 4 shows an enhanced level of alpha(7) selectivity as compared to UB-165 and deschloro UB-165 2. These results are discussed within the context of recent pharmacophore models.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzene Derivatives / chemical synthesis*
Benzene Derivatives / chemistry
Benzene Derivatives / metabolism*
Bridged-Ring Compounds / chemical synthesis*
Bridged-Ring Compounds / chemistry*
Bridged-Ring Compounds / metabolism*
Neurons / metabolism
Nicotinic Agonists / chemical synthesis*
Nicotinic Agonists / metabolism*
Pyridines / chemistry*
Pyridines / metabolism
Radioligand Assay
Rats
Receptors, Nicotinic / drug effects
Receptors, Nicotinic / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

(2-chloro-5-pyridyl)-9-azabicyclo(4.2.1)non-2-ene
Benzene Derivatives
Bridged-Ring Compounds
Nicotinic Agonists
Pyridines
Receptors, Nicotinic