Pyridine ring phenyl analogs

Isoxazole and Isothiazole Derivatives. Bioisosteric replacement of the pyridine ring in nicotine generated a series of novel isoxazole compounds that are selective and potent neuronal nAChR agonists, as exemplified by ABT-418 (71) (Table 14.8) (299). Among the variety of substituents examined at C3 cf the isoxazole, methyl turns out to be optimal, even though other substituents, such as C2-C4 linear alkyl, CF Br, and benzyl (not phenyl), still provide potent analogs. The 3-des-methyl... 

The values of p have been accurately determined for numerous perhydro-l,3-oxazines and their benzo analogs, and the electronic character of a substituent at position 2 can therefore be calculated via Equation (1) by measuring the ring-chain ratios. This principle has been applied to determine the values for numerous substituents X (X = para-situated 1-imidazolyl, 1-benzimidazolyl, 1-benzotriazolyl, 2-benzotriazolyl, and l,2,4-triazolo[2,3- ]pyridin-2-yl) via their 2-(X-phenyl)perhydro-l,3-oxazine derivatives <1997JHG289, 1998MI653>. 

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