Synthesis of Two Fluoro Analogues of the Nicotinic Acetylcholine Receptor Agonist UB-165

• Published in: Journal of organic chemistry 2003-03, Vol.68 (6), p.2475-2478
• Main Authors: Sutherland, Andrew, Gallagher, Timothy, Sharples, Christopher G. V, Wonnacott, Susan
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor; Animals; Binding, Competitive; Brain - metabolism; Bridged-Ring Compounds - chemical synthesis; Bridged-Ring Compounds - chemistry; Bridged-Ring Compounds - pharmacology; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydrocarbons, Fluorinated - chemical synthesis; Molecular Structure; Nicotinic Agonists - chemical synthesis; Nicotinic Agonists - chemistry; Nicotinic Agonists - pharmacology; Organic chemistry; Preparations and properties; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Rats; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo026698b

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 α4β2 and α7 nicotinic receptors.