Synthesis, antinociceptive activity and opioid receptor profiles of 3-(octahydro-1H-pyrano- and -thiopyrano[4,3-c]pyridin-8a-yl)phenols
作者:David E. Bays、Dearg S. Brown、David J. Belton、Jane E. Lloyd、Andrew B. McElroy、Clive A. Meerholz、David I. C. Scopes、Phillip J. Birch、Ann G. Hayes、Michael J. Sheehan
DOI:10.1039/p19890001177
日期:——
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.
一系列新型的顺式和反式-3-(八氢-1 H-吡喃并[4,3 - c ]吡啶-8a-基)苯酚的合成(13a – 1),(15a,b),(20a – d),(21a – e)和反式-3-(八氢-1 H-硫代吡喃并[4,3 - c ]吡啶-8a-基)苯酚(26)进行了描述。1-甲基-4-(3-甲氧基苯基)-1,2,3,6-四氢吡啶的烷基化(7)用2-氯-1-(氯甲氧基)乙烷或2-氯-1-(氯甲氧基)丙烷,然后环化,分别生成双环烯胺(9a)和(9b)。在中性条件下氢化(9a,b)可提供反式融合的八氢吡喃并[4,3- c ]吡啶(10a),(16a)和(17a),而在酸性介质中氢化(9a)得到相应的顺式-融合系统(11a)。的反式-融合octahydrothiopyrano [4,3- Ç ]吡啶(23通过类似的烯胺(22)合成)。经由氯甲酸乙烯酯的N-去甲基化/再烷基化序列引入选择的N-取代基,随