(1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-10-methoxy-12,19-dioxa-4-azahexacyclo[9.6.1.114,17.01,13.05,17.07,18]nonadeca-7(18),8,10-triene | 470458-45-8

• 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,5R,13R,14R,17S)-4-(cyclopropylmethyl)-10-methoxy-12,19-dioxa-4-azahexacyclo[9.6.1.114,17.01,13.05,17.07,18]nonadeca-7(18),8,10-triene
• CAS: 470458-45-8
• 化学式: C₂₁H₂₅NO₃
• 分子量: 339.434
• InChiKey: DDTSVMAYUYFWGK-RLVOKJKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-10-methoxy-12,19-dioxa-4-azahexacyclo[9.6.1.114,17.01,13.05,17.07,18]nonadeca-7(18),8,10-triene 在 N-氯代丁二酰亚胺 、 三乙基硼氢化锂 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 水 、 二甲基亚砜 、 1,1,2,2-四氯乙烷 为溶剂， 反应 50.5h， 生成 (4R,4aS,7aS,12bS)-3-chloro-9-methoxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
  参考文献：
  名称：

  Synthesis of (−)-Homogalanthamine from Naltrexone

  摘要：

  Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from mu opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.

  DOI：

  10.1021/jo1022487
• 作为产物：
  描述：

  纳曲酮 在 吡啶 、 potassium tert-butylate 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.75h， 生成 (1S,5R,13R,14R,17S)-4-(cyclopropylmethyl)-10-methoxy-12,19-dioxa-4-azahexacyclo[9.6.1.114,17.01,13.05,17.07,18]nonadeca-7(18),8,10-triene
  参考文献：
  名称：

  Synthesis of (−)-Homogalanthamine from Naltrexone

  摘要：

  Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from mu opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.

  DOI：

  10.1021/jo1022487

文献信息

• (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof
  申请人：Mallinckrodt LLC

  公开号：US11142502B2

  公开（公告）日：2021-10-12

  The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.

  本发明提供了包含Toll样受体9（TLR9）拮抗剂活性的(+)-吗啡烷，以及使用(+)-吗啡烷治疗疼痛的方法。本发明还提供了包含(+)-吗啡南和阿片激动剂/单胺再摄取抑制剂的药物组合物，以及使用该组合物治疗疼痛的方法。
• (+)-MORPHINANS AS ANTAGONISTS OF TOLL-LIKE RECEPTOR 9 AND THERAPEUTIC USES THEREOF
  申请人：Mallinckrodt LLC

  公开号：US20170029432A1

  公开（公告）日：2017-02-02

  The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.
• US9562014B2
  申请人：——

  公开号：US9562014B2

  公开（公告）日：2017-02-07
• Synthesis of (−)-Homogalanthamine from Naltrexone
  作者：Naoshi Yamamoto、Hideaki Fujii、Satomi Imaide、Shigeto Hirayama、Toru Nemoto、Junji Inokoshi、Hiroshi Tomoda、Hiroshi Nagase

  DOI：10.1021/jo1022487

  日期：2011.4.1

  Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from mu opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.