3-methoxy-6-keto-N-cyclopropylmethyl-normorphinan | 72708-30-6

• 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: 3-methoxy-6-keto-N-cyclopropylmethyl-normorphinan
• 英文别名: 17-cyclobutylmethyl-3-methoxymorphinan-6-one；(1S,9R,10R)-17-(cyclobutylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 72708-30-6
• 化学式: C₂₂H₂₉NO₂
• 分子量: 339.478
• InChiKey: NNUUOAQJUHMLDS-NNWRFLSQSA-N

物化性质

• 沸点：
  496.3±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 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：

  3-methoxy-6-keto-N-cyclopropylmethyl-normorphinan 在 氢溴酸 作用下， 以90%的产率得到(1S,9R,10R)-17-(cyclobutylmethyl)-4-hydroxy-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
• 作为产物：
  描述：

  二氢可待因酮 在 吡啶 、 盐酸 、 氨 、 sodium 、 氯甲酸乙酯 、 铜 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 111.0h， 生成 3-methoxy-6-keto-N-cyclopropylmethyl-normorphinan
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 6,7-Indolo/Thiazolo-MorphinansFurther SAR of Levorphanol

  摘要：

  To further extend the structure-activity relationships of levorphanol, two series of novel morphinans were prepared by incorporation of an indole or aminothiazole fragment to the hexyl ring (ring C) in levorphanol. Such morphinans differed from previously reported ligands in that such indole- or aminothiazole-containing morphinans displayed enhanced binding affinity to the delta opioid receptor, while the affinity to kappa and mu receptors was slightly reduced.

  DOI：

  10.1021/jm0701674

文献信息

• 17-Cycloalkylmethyl-6-methylene-morphinane-derivatives
  申请人：MILES LABORATORIES, INC.

  公开号：EP0027925A1

  公开（公告）日：1981-05-06

  Disclosed are 6-methylene, morphinan compounds corresponding to the formula: wherein R1 und R3 are H or methyl and R2 is cyclopropylmethyl or cyclobutylmethyl. These compounds are useful as mixed analgesics/narcotic antagonists.

  所公开的 6-亚甲基吗啡烷化合物符合以下式子： 其中 R1 和 R3 为 H 或甲基，R2 为环丙基甲基或环丁基甲基。这些化合物可用作混合镇痛剂/麻醉拮抗剂。
• Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists
  作者：Yoshihiro Ida、Toru Nemoto、Shigeto Hirayama、Hideaki Fujii、Yumiko Osa、Masayuki Imai、Takashi Nakamura、Toshiyuki Kanemasa、Akira Kato、Hiroshi Nagase

  DOI：10.1016/j.bmc.2011.11.047

  日期：2012.1

  The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the delta opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the 8 receptor over the mu receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the 5 receptor in the [S-35]GTPyS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the delta receptor among the morphinan derivatives, the agonist activity toward the delta receptor was the most potent for candidates with the 3-hydroxy group. (C) 2011 Elsevier Ltd. All rights reserved.
• Analgesic narcotic antagonists. 9. 6-Methylene-8.beta.-alkyl-N-(cycloalkylmethyl)-3-hydroxy- or -methoxymorphinans
  作者：Joseph O. Polazzi、Michael P. Kotick、John F. Howes、Ann R. Bousquet

  DOI：10.1021/jm00144a029

  日期：1981.12

  Series of N-(cyclopropylmethyl) (P series) or N-(cyclobutylmethyl) (B series) 3-methoxy (1) or 3-hydroxy (2) morphinan-6-ones with hydrogen (a), methyl (b), or ethyl (c) groups in the 8 beta position were converted to the 6-methylene compounds 3 or 4 by reaction with Ph3P = CH2. One member of this new series, N-(cyclobutylmethyl)-8 beta-methyl-6-methylenemorphinan-3-ol (4Bb), had potent mixed agonist-narcotic antagonist properties and, in contrast to the previously studied 6-oxo compound 2Bb, did not substitute for morphine in dependent rats or monkeys.
• 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.
• US4259329A
  申请人：——

  公开号：US4259329A

  公开（公告）日：1981-03-31