(1S,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one | 72747-66-1

• 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: (1S,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 72747-66-1
• 化学式: C₂₁H₂₇NO₂
• 分子量: 325.451
• InChiKey: TVSUSZBGGNVGHO-NRSPTQNISA-N

物化性质

• 沸点：
  483.7±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one 在 sodium tetrahydroborate 、 三溴化硼 、 sodium hydride 作用下， 以 乙醇 、 氯仿 、 苯 为溶剂， 反应 7.5h， 生成
  参考文献：
  名称：

  Novel opiates and antagonists. 5. 7-Carbethoxy-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones

  摘要：

  A direct conversion of deoxydihydrothebaine-phi (1) to 3-methoxymorphinan-6-one (3Ca) and its trans isomer 3Ta was achieved in excellent yield by the catalytic reduction of 1 in AcOH containing CF3COOH. Treatment of 3Ca or 3Ta with NaH and diethyl carbonate formed the corresponding 7-carbethoxy derivatives 4a which, on O-demethylation, furnished the 3-hydroxy compounds 4b. The analgesic N-methyl compounds 3 were converted to the 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 6--8. Two of these compounds, one in the cis (7Ca) and the other in the trans (7Ta) series, showed mixed agonist/antagonist activity in the pentazocine range.

  DOI：

  10.1021/jm00350a020
• 作为产物：
  描述：

  C₁₈H₂₀N₂O₂ 在 盐酸 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1S,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
  参考文献：
  名称：

  止痛麻醉剂。2. 8-烷基吗啡喃-6-。

  摘要：

  通过将二烷基铜酸锂共轭添加到相应的7,8-二氢-6-烷基中来制备一系列的8-烷基-3-甲氧基-17-甲基吗啡喃-6-（3C）和-异吗啡喃-6-酮（3T）。 2C和2T。这些17-甲基化合物是有效的镇痛药，并通过用环烷基甲基部分取代17-甲基而转化为混合的麻醉激动剂-拮抗剂7-10。8个取代基改变了观察到的活性类型。这些化合物之一，即17-（环丁基甲基）-3-羟基-8β-甲基吗啡喃-6-（10Ca）的激动剂与拮抗剂之比为0.1。化合物10Ca在大鼠中不支持或不引起依赖性。然而，该化合物似乎是吗啡依赖性猴子中的典型麻醉剂。

  DOI：

  10.1021/jm00176a013

文献信息

• Novel opiates and antagonists. 6. 7-Alkyl-6,7-didehydromorphinans
  作者：James Quick、Patricia Herlihy、John F. Howes

  DOI：10.1021/jm00371a013

  日期：1984.5

  A method for preparing a variety of 7-alkyl-6,7- didehydromorphinans from the corresponding 6- morphinanones is described. The key intermediates in this sequence are the 7-formyl derivatives. The two epimeric B/C-trans-7-(1- hydroxypentyl ) morphinans ( 16a ,b) are stereochemically similar to the endo- ethanotetrahydrooripavines and are extremely potent in the mouse writhing test. The corresponding B/C-cis -7-(1- hydroxypentyl ) morphinans are inactive in this test.
• US4423221A
  申请人：——

  公开号：US4423221A

  公开（公告）日：1983-12-27
• Novel opiates and antagonists. 5. 7-Carbethoxy-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones
  作者：Patricia Herlihy、Haldean C. Dalzell、John F. Howes、Raj K. Razdan

  DOI：10.1021/jm00350a020

  日期：1982.8

  A direct conversion of deoxydihydrothebaine-phi (1) to 3-methoxymorphinan-6-one (3Ca) and its trans isomer 3Ta was achieved in excellent yield by the catalytic reduction of 1 in AcOH containing CF3COOH. Treatment of 3Ca or 3Ta with NaH and diethyl carbonate formed the corresponding 7-carbethoxy derivatives 4a which, on O-demethylation, furnished the 3-hydroxy compounds 4b. The analgesic N-methyl compounds 3 were converted to the 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 6--8. Two of these compounds, one in the cis (7Ca) and the other in the trans (7Ta) series, showed mixed agonist/antagonist activity in the pentazocine range.
• Analgesic narcotic antagonists. 2. 8-Alkylmorphinan-6-ones
  作者：Joseph O. Polazzi、Robert N. Schut、Michael P. Kotick、John F. Howes、Patricia F. Osgood、Raj K. Razdan、Julian E. Villarreal

  DOI：10.1021/jm00176a013

  日期：1980.2

  -isomorphinan-6-ones (3T) were prepared by conjugate addition of lithium dialkylcuprates to the corresponding 7,8-didehydro-6-ones 2C and 2T. These 17-methyl compounds were potent analgesics and were converted to mixed narcotic agonists-antagonists 7-10, by replacement of the 17-methyl groups with cycloalkylmethyl moieties. The 8 substituent modified the type of activity observed. One of these compounds

  通过将二烷基铜酸锂共轭添加到相应的7,8-二氢-6-烷基中来制备一系列的8-烷基-3-甲氧基-17-甲基吗啡喃-6-（3C）和-异吗啡喃-6-酮（3T）。 2C和2T。这些17-甲基化合物是有效的镇痛药，并通过用环烷基甲基部分取代17-甲基而转化为混合的麻醉激动剂-拮抗剂7-10。8个取代基改变了观察到的活性类型。这些化合物之一，即17-（环丁基甲基）-3-羟基-8β-甲基吗啡喃-6-（10Ca）的激动剂与拮抗剂之比为0.1。化合物10Ca在大鼠中不支持或不引起依赖性。然而，该化合物似乎是吗啡依赖性猴子中的典型麻醉剂。