Synthesis of two fluoro analogues of the nicotinic acetylcholine receptor agonist UB-165.
Two racemic fluoropyridine analogues 4 and 5 of the potent nicotinic agonist UB-165 have been synthesized. Halogenated pyridines 7 and 12 provided the organometallic reagents needed for the Negishi and Suzuki coupling reactions used for the preparation of 4 and 5, and the N-vinyloxycarbonyl protecting group of 8 and 15 was cleaved using a novel trifluoroacetic acid-mediated deprotection protocol. Analogue 4 retained high binding affinity at rat brain alpha4beta2 and alpha7 nicotinic receptors.
Sutherland
Andrew
A
School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom.
Gallagher
Timothy
T
Sharples
Christopher G V
CG
Wonnacott
Susan
S
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis*; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
C407663:(2-chloro-5-pyridyl)-9-azabicyclo(4.2.1)non-2-ene; D001952:Bridged-Ring Compounds; C579165:Chrna7 protein, rat; D006845:Hydrocarbons, Fluorinated; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2