Synthesis and Nicotinic Binding of Novel Phenyl Derivatives of UB‐165. Identifying Factors Associated with α7 Selectivity.

Abstract

Multi-membered N-heterocycles R 0690 Synthesis and Nicotinic Binding of Novel Phenyl Derivatives of UB-165. Identifying Factors Associated with α7 Selectivity. -Four racemic, phenyl-substituted analogues of the potent nicotinic agonist UB-165 (VId) are synthesized by means of a key Negishi coupling reaction of versatile enol triflate (II) with appropriate bromopyridine derivatives. Results of nicotinic binding studies indicate that compound (VIa) shows an enhanced level of α 7 selectivity as compared to UB-165. -(KARIG, G.; LARGE, J. M.; SHARPLES, C. G. V.; SUTHERLAND, A.; GALLAGHER*, T.; WONNACOTT, S.; Bioorg. Med. Chem. Lett. 13 (2003) 17, 2825-2828; Sch. Chem., Univ. Bristol, Cantock's Close, Bristol BS8 1TS, UK; Eng.) -M. Schroeter 46-172

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

“…Presentation of functional activity of nicotinic agonists is beyond the scope of this review. (Gohlke et al, 2002(Gohlke et al, , 2003Karig et al, 2003).…”

“…13, as exemplified by U-165 (Wright et al, 1997;Sharples et al, 2002;Karig et al, 2003;Sutherland et al, 2003). The laevorotatory enantiomer (−)-U-165 had a 14-fold higher affinity for α 4 β 2 receptors than the dextro-rotatory enantiomer (+)-U-165.…”

QSAR study of a large set of 3-pyridyl ethers as ligands of the α4β2 nicotinic acetylcholine receptor

“…Currently, the analogues of A-85380 (3-pyridyl ethers analogues) have been becoming the focus in the development of nAChR ligands. A large diversity of 3-pyridyl ether analogues have been synthesized based on bioisosteric substitution in the past decades [10][11][12][13][14][15][16][17]. Some of them evenly obtained an affinity at pM magnitude.…”