Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with alpha7 selectivity.
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.
Karig
Gunter
G
School of Chemistry, University of Bristol, UK.
Large
Jonathan M
JM
Sharples
Christopher G V
CG
Sutherland
Andrew
A
Gallagher
Timothy
T
Wonnacott
Susan
S
D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C407663:(2-chloro-5-pyridyl)-9-azabicyclo(4.2.1)non-2-ene; D001555:Benzene Derivatives; D001952:Bridged-Ring Compounds; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic