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)sulfanyl]-1-methylpiperidine ( 3a ) and its demethylation led to the deazaanpirtoline ( 3c ). Nucleophilic substitution of piperidine-4-thiole with 2-chloro-4-nitropyridine, 2,4-dichloro-6-methylpyridine, and 3,6-dichloropyridazine led to 2-chloro-4-(piperidin-4-ylsulfanyl)pyridine ( 6 ), 4-chloro-6-methyl-2-(piperidin-4-ylsulfanyl)pyridine ( 7 ), and 3-chloro-6-(piperidin-4-ylsulfanyl)pyridazine ( 8 ), respectively. 2-Chloro-6-(pyridin-4-ylsulfanyl)pyridine ( 10 ) and 4-[(2-chloropyridin-6-yl)sulfanyl]quinoline ( 11 ) were obtained from sodium 2-chloropyridine-6-thiolate. Homoanpirtoline analogs with methylene group inserted between the pyridine moiety and the sulfur atom (compound 12b ) as well as between the sulfur atom and the piperidine ring (compound 13b ) were also prepared.