Molecular modification of anpirtoline, a non-opioid centrally acting analgesic

Molecular modification of anpirtoline (2a) is described. Several methods of preparation of 4-[(3-chlorophenyl)suIfanyl]-1-methylpiperidine (3a) and it s demethylation led to the deazaanpirtoline (3c). Nucleophilic substitution of piperidine-4-thiole with 2-chloro-4-nitropyridine, 2,4-dichloro-6-methy lpyridine, and 3,6-dichloropyridazine led to 2-chloro-4-(piperidin-4-ylsulf anyl)pyridine (6), 4-chloro-6-methyl-2-(pipelidin-4-ylsulfanyl)pyridine (7) , and 3-chloro-6-(piperidin-4-ylsulfanyl)pyridazine (8), respectively. 2-Ch loro-6-(pyridin-4-ylsulfanyl)pyridine (10) and 4-[(2-chloropyridin-6-yl)sul fanyl] quinoline (11) were obtained from sodium 2-chloropyridine-6-thiolate . Homoanpirtoline analogs with methylene group inserted between the pyridin e moiety and the sulfur atom (compound 12b) as well as between the sulfur a tom and the piperidine ring (compound 13b) were also prepared.