1. Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with alpha7 selectivity.
- Author
-
Karig G, Large JM, Sharples CG, Sutherland A, Gallagher T, and Wonnacott S
- Subjects
- Animals, Benzene Derivatives chemistry, Neurons metabolism, Pyridines metabolism, Radioligand Assay, Rats, Receptors, Nicotinic drug effects, Receptors, Nicotinic metabolism, Stereoisomerism, Structure-Activity Relationship, Benzene Derivatives chemical synthesis, Benzene Derivatives metabolism, Bridged-Ring Compounds chemical synthesis, Bridged-Ring Compounds chemistry, Bridged-Ring Compounds metabolism, Nicotinic Agonists chemical synthesis, Nicotinic Agonists metabolism, Pyridines chemistry
- 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.
- Published
- 2003
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