阿片受体介导现象的探针。40. N-取代的顺式-4a-乙基-1,2,3,4,4a,9a-六氢苯并呋喃[2,3-c]吡啶-8-醇。
Probes for narcotic receptor mediated phenomena. 40. N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols.
机构信息
Drug Design and Synthesis Section, Department of Health and Human Services, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
出版信息
Bioorg Med Chem. 2010 Jan 1;18(1):91-9. doi: 10.1016/j.bmc.2009.11.022. Epub 2009 Nov 18.
Abstract
A series of N-substituted rac-cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols have been prepared using a simple synthetic route previously designed for synthesis of related cis-2-methyl-4a-alkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols. The new phenolic compounds, where the aromatic hydroxy moiety is situated ortho to the oxygen atom in the oxide-bridged ring, do not interact as well as the pyridin-6-ols with opioid receptors. The N-para-fluorophenethyl derivative had the highest mu-opioid receptor affinity of the examined compounds (K(i)=0.35 microM).
摘要
已使用先前设计用于合成相关顺式-2-甲基-4a-烷基-1,2,3,4,4a,9a-六氢苯并呋喃并[2,3-c]吡啶-6-醇的简单合成路线制备了一系列 N-取代的外消旋顺式-4a-乙基-1,2,3,4,4a,9a-六氢苯并呋喃并[2,3-c]吡啶-8-醇。新的酚类化合物中，芳香羟基部分位于氧化物桥环的氧原子的邻位，与阿片受体的相互作用不如吡啶-6-醇那样好。在所检查的化合物中，N-对氟苯乙基衍生物具有最高的μ-阿片受体亲和力（K(i)=0.35 μM）。
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