Collect. Czech. Chem. Commun.
1999, 64, 363-376
https://doi.org/10.1135/cccc19990363
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
Abstract
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.
