Nonclassical nicotine antagonists

Article abstract of DOI:10.1021/jm00245a028

A series of 'nonclassical' nicotine antagonists was synthesized and compared to the 'classical' nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure activity relationship of this class of compounds are discussed.