17-cyclopropylmethyl-3-methoxy-14β-hydroxy-4,5α-epoxy-6β-mercaptomorphinan | 1092370-08-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 17-cyclopropylmethyl-3-methoxy-14β-hydroxy-4,5α-epoxy-6β-mercaptomorphinan
• 英文别名: 17-Cyclopropylmethyl-4,5alpha-epoxy-14beta-hydroxy-3-methoxy-6beta-mercaptomorphinan；(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-methoxy-7-sulfanyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-ol
• CAS: 1092370-08-5
• 化学式: C₂₁H₂₇NO₃S
• 分子量: 373.516
• InChiKey: URGGNVVBPIPXCY-RLVOKJKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  42.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  17-cyclopropylmethyl-3-methoxy-14β-hydroxy-4,5α-epoxy-6β-mercaptomorphinan 、 己酰氯 在 sodium sulfate 作用下， 以 水 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship of novel opioid κ-agonists

  摘要：

  By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa- gonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.011
• 作为产物：
  描述：

  S-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a-hydroxy-9-methoxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] ethanethioate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以718 mg的产率得到17-cyclopropylmethyl-3-methoxy-14β-hydroxy-4,5α-epoxy-6β-mercaptomorphinan
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship of novel opioid κ-agonists

  摘要：

  By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa- gonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.011

文献信息

• Brain cell protective agent
  申请人：Toray Industries, Ltd.

  公开号：US05972953A1

  公开（公告）日：1999-10-26

  The present invention relates to a novel brain cell protective agent having for its active ingredient a morphinan derivative represented with Compound 1 ##STR1## or pharmacologically acceptable acid addition salt thereof. The compounds used in the present invention were found to have excellent defensive effects against brain nerve cell necrosis in both in vitro and in vivo pharmacological evaluations, and can be used as useful preventive and therapeutic agents of ischemic brain disorders, brain nerve cell disorders and dementia.

  本发明涉及一种新型脑细胞保护剂，其活性成分为一种吗啡类衍生物，用化合物1表示，或其药理学上可接受的酸盐。本发明中使用的化合物在体外和体内药理评价中表现出对脑神经细胞坏死的优异防御效果，并可用作缺血性脑疾病、脑神经细胞疾病和痴呆症的有用预防和治疗剂。
• Morphinan derivatives and pharmaceutical use thereof
  申请人：Toray Industries, Inc.

  公开号：US06177438B1

  公开（公告）日：2001-01-23

  A morphinan derivative or its pharmaceutically acceptable acid addition salt represented with, for example, and an analgesic, diuretic, antitussive and brain cell protector having its derivative or its salt as the active ingredient are described. The compound of the present invention possesses strong analgesic activity, diuretic action and antitussive action as a highly selective &kgr;-opioid agonist, allowing it to be used as a useful analgesic, diuretic and antitussive. On the other hand, the compound of the present invention also possesses remarkable cerebro-neuroprotective activity, thus allowing it be used as a useful cerebro-neuroprotective agents.

  描述了一种吗啡样衍生物或其药学上可接受的酸加成盐，例如作为镇痛剂、利尿剂、镇咳剂和脑细胞保护剂的活性成分的衍生物或其盐。本发明化合物具有强烈的镇痛、利尿和镇咳作用，作为高度选择性的κ-阿片受体激动剂，可用作有用的镇痛剂、利尿剂和镇咳剂。另一方面，本发明化合物也具有显著的脑神经保护活性，因此可用作有用的脑神经保护剂。
• BRAIN CELL PROTECTIVE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0661283A1

  公开（公告）日：1995-07-05

  A novel brain cell protective containing a morphinane derivative represented by the compound of formula (1) or a pharmacologically acceptable acid-addition salt thereof as the active ingredient. This compound exhibits an excellent protective effect against cranial nerve cell necrosis in both in vitro and in vivo pharmacological tests, and hence can be used for preventing or treating ischemic encephalopathy, cranial nerve cell disorder, and dementia.

  一种新型脑细胞保护剂，含有以式（1）化合物或其药理学上可接受的酸加成盐为代表的吗啡烷衍生物作为活性成分。该化合物在体外和体内药理试验中对颅神经细胞坏死均有很好的保护作用，因此可用于预防或治疗缺血性脑病、颅神经细胞紊乱和痴呆症。
• MORPHINAN DERIVATIVE AND MEDICINAL USE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0663401A1

  公开（公告）日：1995-07-19

  A morphinan derivative represented by formula (1) or a pharmacologically acceptable acid-addition salt thereof, and analgesic, diuretic, antitussive and brain cell protective agents each containing the derivative or the salt as the active ingredient. These compounds have potent analgesic, diuretic and antitussive effects as a highly selective κ-opioid agonist, and are useful as analgesic, diuretic and antitussive agents. In addition, they have a significant brain cell protective effect and are useful as a brain cell protective agent.

  由式（1）代表的吗啡南衍生物或其药理学上可接受的酸加成盐，以及含有该衍生物或盐作为活性成分的镇痛剂、利尿剂、镇咳剂和脑细胞保护剂。这些化合物作为一种高选择性κ-类阿片激动剂，具有强效的镇痛、利尿和镇咳作用，可用作镇痛、利尿和镇咳制剂。此外，它们还具有明显的脑细胞保护作用，可用作脑细胞保护剂。
• US5972953A
  申请人：——

  公开号：US5972953A

  公开（公告）日：1999-10-26