Collect. Czech. Chem. Commun. 1999, 64, 363-376

Molecular Modification of Anpirtoline, a Non-Opioid Centrally Acting Analgesic

Stanislav Rádl*, Wieland Hafner, Petr Hezký, Ivan Krejčí, Jan Proška and Jan Taimr

Research Institute of Pharmacy and Biochemistry, 130 60 Prague 3, Czech Republic


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.

Keywords: Anpirtoline; 4-Phenylsulfanylpiperidines; Piperidines; Pyridines; Analgesic activity; Analgesics; 5-HT receptor ligands.