用于麻醉受体介导现象的探针。39. 对映体N-取代苯并呋喃并[2,3-c]吡啶-6-醇：合成及其与氧化物桥连苯吗喃的拓扑关系。
Probes for narcotic receptor mediated phenomena. 39. Enantiomeric N-substituted benzofuro[2,3-c]pyridin-6-ols: synthesis and topological relationship to oxide-bridged phenylmorphans.
作者信息
Zhang Yi, Lee Yong Sok, Rothman Richard B, Dersch Christina M, Deschamps Jeffrey R, Jacobson Arthur E, Rice Kenner C
机构信息
Department of Health and Human Services, Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9415, USA.
出版信息
J Med Chem. 2009 Dec 10;52(23):7570-9. doi: 10.1021/jm9004225.
Abstract
Enantiomers of N-substituted benzofuro[2,3-c]pyridin-6-ols have been synthesized, and the subnanomolar affinity and potent agonist activity of the known racemic N-phenethyl substituted benzofuro[2,3-c]pyridin-6-ol can now be ascribed to the 4aS,9aR enantiomer. The energy-minimized structures suggest that the active enantiomer bears a greater three-dimensional resemblance to morphine than to an ostensibly structurally similar oxide-bridged phenylmorphan. Structural features of the conformers of N-substituted benzofuro[2,3-c]pyridin-6-ols were compared to provide the rationale for their binding affinity.
摘要
已合成了N-取代苯并呋喃并[2,3-c]吡啶-6-醇的对映体，已知的外消旋N-苯乙基取代苯并呋喃并[2,3-c]吡啶-6-醇的亚纳摩尔亲和力和强效激动剂活性现在可归因于4aS,9aR对映体。能量最小化结构表明，活性对映体与吗啡的三维相似性大于与表面结构相似的氧化物桥连苯基吗啡烷的相似性。比较了N-取代苯并呋喃并[2,3-c]吡啶-6-醇构象异构体的结构特征，以解释它们的结合亲和力。
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