(1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indol-11-ol

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - Oxamorphinans
• 英文名称: (1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indol-11-ol
• 英文别名: (1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-11H-6,11b-(epiminoethano)-1,5a-epoxynaphtho[1,2-e]indol-11-ol；(1R,2S,3S,6R,9S,10R)-5-benzyl-20-(cyclopropylmethyl)-15-methoxy-21-oxa-5,20-diazahexacyclo[8.7.3.13,9.01,9.02,6.012,17]henicosa-12(17),13,15-trien-16-ol
• 化学式: C₃₀H₃₆N₂O₃
• 分子量: 472.627
• InChiKey: ATWOULURADQPPU-XZDBJEHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indol-11-ol 在 吡啶 、 铜 、 potassium carbonate 、 乙二胺 作用下， 以 四氢呋喃 为溶剂， 生成 (1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indole
  参考文献：
  名称：

  Novel delta opioid receptor agonists with oxazatricyclodecane structure showing potent agonistic activities

  摘要：

  We recently reported oxazatricyclodecane derivatives 1 as delta opioid receptor (DOR) agonists having a novel chemotype, but their DOR agonistic activities were relatively low. Based on the working hypothesis that the dioxamethylene moiety in 1 may be an accessory site and that it may interfere with the sufficient conformational change of the receptor required for exerting the full agonistic responses, we designed and synthesized new oxazatricyclodecane derivatives 2-4 lacking the dioxamethylene moiety. As we expected, the designed compounds 2-4 showed pronouncedly improved agonistic activities for the DOR. Compound 2a with the 17-cyclopropylmethyl substituent was a potent agonist with the highest selectivity for the DOR and was expected to be a lead compound for novel and selective DOR agonists. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.059
• 作为产物：
  描述：

  (1S,3aS,5aS,6R,11bR,11cR)-3-benzyl-14-(cyclopropylmethyl)-3a,11-dihydroxy-10-methoxy-1,3,3a,4,5,6,7,11c-octahydro-2H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indol-2-one 在 硼烷四氢呋喃络合物 、 盐酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以94%的产率得到(1S,3aR,5aS,6R,11bR,11cS)-3-benzyl-14-(cyclopropylmethyl)-10-methoxy-2,3,3a,4,5,6,7,11c-octahydro-1H-6,11b-(iminoethano)-1,5a-epoxynaphtho[1,2-e]indol-11-ol
  参考文献：
  名称：

  MORPHINAN DERIVATIVE

  摘要：

  公开号：

  EP2774926B1

文献信息

• MORPHINAN DERIVATIVE
  申请人：The Kitasato Institute

  公开号：EP2774926B1

  公开（公告）日：2017-03-15
• US20140343015A1
  申请人：——

  公开号：US20140343015A1

  公开（公告）日：2014-11-20
• US8952030B2
  申请人：——

  公开号：US8952030B2

  公开（公告）日：2015-02-10
• US9624223B2
  申请人：——

  公开号：US9624223B2

  公开（公告）日：2017-04-18
• Novel delta opioid receptor agonists with oxazatricyclodecane structure showing potent agonistic activities
  作者：Kohei Hayashida、Shigeto Hirayama、Takashi Iwai、Yoshikazu Watanabe、Toshihiro Takahashi、Junichi Sakai、Eriko Nakata、Tomio Yamakawa、Hideaki Fujii、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2017.04.059

  日期：2017.6

  We recently reported oxazatricyclodecane derivatives 1 as delta opioid receptor (DOR) agonists having a novel chemotype, but their DOR agonistic activities were relatively low. Based on the working hypothesis that the dioxamethylene moiety in 1 may be an accessory site and that it may interfere with the sufficient conformational change of the receptor required for exerting the full agonistic responses, we designed and synthesized new oxazatricyclodecane derivatives 2-4 lacking the dioxamethylene moiety. As we expected, the designed compounds 2-4 showed pronouncedly improved agonistic activities for the DOR. Compound 2a with the 17-cyclopropylmethyl substituent was a potent agonist with the highest selectivity for the DOR and was expected to be a lead compound for novel and selective DOR agonists. (C) 2017 Elsevier Ltd. All rights reserved.