Collect. Czech. Chem. Commun. 1999, 64, 377-388

Synthesis and Antinociceptive Activity of Some 3-Chlorophenyl- and 6-Chloropyridin-2-yl Derivatives

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

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


Derivatives of 2-chloro-6-(4-hydroxy-1-methylpiperidin-4-yl)pyridine (2b) were prepared and tested as analgesics. 2-Chloro-6-lithiopyridine treated with quinuclidin-3-one, 1-methylpyrrolidin-3-one, 2-(dimethylaminomethyl)cyclohexanone, and ethyl 1-methylpiperidin-4-ylcarboxylate provided the corresponding alcohols 5, 6, 13a, and 6-chloro-2-pyridyl 1-methylpiperidin-4-yl ketone (9). The ketone was reduced with sodium borohydride or treated with methylmagnesium chloride or phenyllithium to provide the corresponding alcohols 11, 12a and 12b, respectively. 1-[4-(6-Chloro-2-pyridyl)1-methylpiperidin-4-yl]-1-methylethanol (4b) was prepared from 2-chloro-6-(1-methyl-1,2,5,6-tetrahydropyridin-4-yl)pyridine (14b) by treatment with butyllithium and acetone followed by reduction of intermediate 15b with sodium cyanoborohydride.

Keywords: Anpirtoline; Piperidines; Pyridines; Phenylpiperidines; (Pyridin-2-yl)piperidines; Analgesic activity; Analgesics.