Issue 7, 1989

Synthesis, antinociceptive activity and opioid receptor profiles of 3-(octahydro-1H-pyrano- and -thiopyrano[4,3-c]pyridin-8a-yl)phenols

Abstract

The synthesis of a series of novel cis- and trans-3-(octahydro-1H-pyrano[4,3-c]pyridin-8a-yl)phenols (13a1), (15a, b), (20ad), (21ae) and the trans-3-(octahydro-1H-thiopyrano[4,3-c]pyridin-8a-yl)phenol (26) is described. Alkylation of 1-methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine (7) with 2-chloro-1-(chloromethoxy)ethane or 2-chloro-1-(chloromethoxy)propane, and subsequent cyclization, generated the bicyclic enamines (9a) and (9b) respectively. Hydrogenation of (9a, b) under neutral conditions provided the trans-fused octahydropyrano[4,3-c]pyridines (10a), (16a), and (17a), whereas hydrogenation of (9a) in acidic media gave the corresponding cis-fused system (11a). The trans-fused octahydrothiopyrano[4,3-c]pyridine (23) was synthesized via the analogous enamine (22). Selected N-substituents were introduced via a vinyl chloroformate N-demethylation/re-alkylation sequence and subsequent O-demethylation afforded the title phenols. The antinociceptive activity and opioid receptor profile of these compounds has been determined and structure activity relationships are discussed.

Article information

Article type
Paper

J. Chem. Soc., Perkin Trans. 1, 1989, 1177-1186

Synthesis, antinociceptive activity and opioid receptor profiles of 3-(octahydro-1H-pyrano- and -thiopyrano[4,3-c]pyridin-8a-yl)phenols

D. E. Bays, D. S. Brown, D. J. Belton, J. E. Lloyd, A. B. McElroy, C. A. Meerholz, D. I. C. Scopes, P. J. Birch, A. G. Hayes and M. J. Sheehan, J. Chem. Soc., Perkin Trans. 1, 1989, 1177 DOI: 10.1039/P19890001177

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