4aS,9aR-(-)-cis-4a-ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol | 1182348-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 4aS,9aR-(-)-cis-4a-ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol
• 英文别名: (4aS,9aR)-4a-ethyl-2-methyl-1,3,4,9a-tetrahydro-[1]benzofuro[2,3-c]pyridin-6-ol
• CAS: 1182348-88-4
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: WYHZNSRQYYJYTK-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4aS,9aR-(-)-cis-4a-ethyl-6-methoxy-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridine 在 氢溴酸 作用下， 以 水 为溶剂， 以93%的产率得到4aS,9aR-(-)-cis-4a-ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol
  参考文献：
  名称：

  麻醉受体介导的现象的探针。39.(1) 对映体 N-取代的苯并呋喃 [2,3-c]pyridin-6-ols：与氧化物桥接苯基吗啡烷的合成和拓扑关系 (2)†

  摘要：

  N-取代的苯并呋喃[2,3 - c ]pyridin-6-ols的对映异构体已经合成，已知的外消旋N-苯乙基取代的苯并呋喃[2,3 - c ]pyridin-6-具有亚纳摩尔亲和力和有效的激动剂活性。ol 现在可以归因于 4a S ,9a R对映异构体。能量最小化的结构表明活性对映体与吗啡的三维相似性比表面上结构相似的氧化物桥接苯基吗啡更相似。比较了 N-取代的苯并呋喃 [2,3 - c ]pyridin-6-ol的构象异构体的结构特征，以提供其结合亲和力的基本原理。

  DOI：

  10.1021/jm9004225

文献信息

• Benzofuro[2,3-c]pyridin-6-ols: synthesis, affinity for opioid-receptor subtypes, and antinociceptive activity
  作者：Alan J. Hutchison、Reynalda De Jesus、Michael Williams、John P. Simke、Robert F. Neale、Robert H. Jackson、Francis Ambrose、Beverly J. Barbaz、Matthew A. Sills

  DOI：10.1021/jm00129a031

  日期：1989.9

  A general synthetic approach to a novel series of cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols is described together with their receptor-binding profile on opioid-receptor subtypes (mu, kappa, delta). In addition, their in vivo antinociceptive activity was assessed. A number of the analogues synthesized showed potent affinity for opioid receptors and have potent antinociceptive activity in a mouse phenylquinone abdominal stretching model. In addition, the SAR for nitrogen substitution in the above series is explored with respect to the overall opioid receptor subtype binding profile. In general it was found that substituents which enhanced mu and kappa binding affinity in the benzomorphan series had a similar effect in the benzofuropyridine series described in this manuscript. An overlap hypothesis topologically connecting the benzomorphan nucleus to the cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridine nucleus is also presented.
• Probes for Narcotic Receptor Mediated Phenomena. 38. An Expeditious Synthesis of rac-cis-4a-Ethyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol and rac-cis-2-Methyl-4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol
  作者：Kenner C. Rice、Arthur E. Jacobson、Malliga R. Iyer、Jeffrey R. Deschamps

  DOI：10.3987/com-09-s(d)84

  日期：——

  A high-yielding five-step synthesis of cis-benzofuropyridin-6-ols provided an improved route to compounds with low to subnanomolar affinity at opioid receptors and high antinociceptive potency. This synthesis provided the known rac-cis-4a-etbyl-2-methyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3c]pyridin-6-ol (1a) in high yield, and the novel rac-cis-2-methyl-4a-phenethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ol (1b). It was achieved using NBS to prepare the key intermediate 7. Di-demethylation followed by subsequent displacement of the bromine by the phenolic ion in hot Et3N gave the desired 1a. The structure of la was confirmed by X-ray crystallography.
• Probes for Narcotic Receptor Mediated Phenomena. 39. Enantiomeric N-Substituted Benzofuro[2,3-<i>c</i>]pyridin-6-ols: Synthesis and Topological Relationship to Oxide-Bridged Phenylmorphans
  作者：Yi Zhang、Yong Sok Lee、Richard B. Rothman、Christina M. Dersch、Jeffrey R. Deschamps、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm9004225

  日期：2009.12.10

  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

  N-取代的苯并呋喃[2,3 - c ]pyridin-6-ols的对映异构体已经合成，已知的外消旋N-苯乙基取代的苯并呋喃[2,3 - c ]pyridin-6-具有亚纳摩尔亲和力和有效的激动剂活性。ol 现在可以归因于 4a S ,9a R对映异构体。能量最小化的结构表明活性对映体与吗啡的三维相似性比表面上结构相似的氧化物桥接苯基吗啡更相似。比较了 N-取代的苯并呋喃 [2,3 - c ]pyridin-6-ol的构象异构体的结构特征，以提供其结合亲和力的基本原理。