3-methoxy-17-methylmorphinan-6-one | 2246-20-0

• 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-17-methylmorphinan-6-one
• 英文别名: Desoxy-dihydrothebainon；(1S,9R,10R)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 2246-20-0
• 化学式: C₁₈H₂₃NO₂
• 分子量: 285.386
• InChiKey: FCJHDGUWJDXJKI-JQHSSLGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 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-17-methylmorphinan-6-one 在 ethyl chloroformate 、 氢溴酸 、 溴 、 sodium acetate 、 三溴化硼 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 18.0h， 生成 6,7-(2-N-methyl)aminothiazolo-N-cyclopropylmethyl-morphin-3-ol
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Aminothiazolomorphinans at the Mu and Kappa Opioid Receptors

  摘要：

  Previous studies with aminothiazolomorphinans suggested that this class of opioid ligands may be useful as a potential pharmacotherapeutic to decrease drug abuse. Novel aminothiazole derivatives of cyclorphan were prepared to evaluate a series of aminothiazolomorphinans with, varying pharmacological properties at the kappa opioid receptor (KOR) and mu opioid receptor (MOR). This study was focused on exploring the regioisomeric analogs with the aminothiazole on the C-ring of the morphinan skeleton. Receptor binding and [S-35]GTP gamma S binding assays were used to characterize the affinity and pharmacological properties of the aminothiazolomorphinans. Intracranial self-stimulation (ICSS) was used to compare the effects of a representative aminothiazolomorphinan with the morphinan mixed-KOR/MOR agonist butorphan (MCL-101) on brain-stimulation reward.

  DOI：

  10.1021/jm401290y
• 作为产物：
  描述：

  二氢可待因酮 在 吡啶 、 盐酸 、 氨 、 sodium 、 铜 、 caesium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 甲苯 、 苯 为溶剂， 反应 15.0h， 生成 3-methoxy-17-methylmorphinan-6-one
  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

• Rapid access to morphinones: removal of 4,5-ether bridge with Pd-catalyzed triflate reduction
  作者：Christopher D. Hupp、John L. Neumeyer

  DOI：10.1016/j.tetlet.2010.02.146

  日期：2010.4

  A new synthetic method for the removal of the 4,5-bridged ether moiety of several opioids has been developed. This process offers a faster, simpler synthetic route to obtain the morphinone scaffold in high yields without the need for protection of the ketone moiety.

  已经开发出一种用于去除几种阿片类药物的 4,5-桥接醚部分的新合成方法。该过程提供了一种更快、更简单的合成途径，以高产率获得吗啡酮支架，而无需保护酮部分。
• [EN] MORPHINAN DERIVATIVES FOR THE TREATMENT OF NEUROPATHIC PAIN<br/>[FR] DÉRIVÉS DE MORPHINANE POUR LE TRAITEMENT DE LA DOULEUR NEUROPATHIQUE
  申请人：NEKTAR THERAPEUTICS

  公开号：WO2016182840A1

  公开（公告）日：2016-11-17

  The present invention relates to compounds and their use as ligands for mu opioid receptors. Also included are methods for preparing the compounds and pharmaceutical compositions containing the compounds. In one or more embodiments of the invention, a compound according to Formula I is provided: and pharmaceutically acceptable salts thereof, wherein R1-R11 are as described herein.

  本发明涉及化合物及其用作阿片μ受体的配体的应用。还包括制备这些化合物的方法和包含这些化合物的药物组合物。在发明的至少一个实施例中，提供了一种根据公式I的化合物：及其药用可接受的盐，其中R1-R11如本文所述。
• 7-Methyl-8.beta.-lower alkyl or 7-methyl-8-lower alkyl B/C cis or trans
  申请人：Miles Laboratories, Inc.

  公开号：US04230712A1

  公开（公告）日：1980-10-28

  Disclosed are 7-methyl, 8.beta.-lower alkyl and 7 methyl-8-lower alkyl substituted B/C Cis or Trans morphinan-6-one compounds characterized by the structural formula: ##STR1## Specific compounds, included within the scope of the foregoing general formula wherein R.sub.1 is H or methyl, R.sub.2 is cyclopropylmethyl or cyclobutylmethyl, R.sub.3 is H, methyl, ethyl or n-propyl and R.sub.4 is H or methyl are useful as mixed analgesics/narcotic antagonists.

  揭示了具有以下结构式的7-甲基，8.beta.-较低烷基和7-甲基-8-较低烷基取代的B/C顺式或反式吗啡酮化合物：具体化合物包括在上述一般式范围内，其中R.sub.1为H或甲基，R.sub.2为环丙基甲基或环丁基甲基，R.sub.3为H，甲基，乙基或正丙基，R.sub.4为H或甲基，可用作混合镇痛剂/麻醉拮抗剂。
• [EN] SPIROCYCLIC MORPHINANS AND USE THEREOF<br/>[FR] MORPHINANES SPIROCYCLIQUES ET UTILISATION ASSOCIÉE
  申请人：PURDUE PHARMA LP

  公开号：WO2015183780A1

  公开（公告）日：2015-12-03

  In one aspect, the invention provides compounds of Formula I: (I) and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, Y, Za are defined as set forth in the disclosure. The invention also provides compounds of any one of Formulae II to VII, IA to IC, and IIA to IIC, and pharmaceutically acceptable salts and solvates thereof. Other aspects of the invention include the use of compounds of Formulae I to VII, IA to IC, and IIA to IIC, and pharmaceutically acceptable salts and solvates thereof for the treatment of disorders responsive to modulation of one or more opioid receptors. In certain embodiments, the Compounds of the Invention are useful for treating pain.

  本发明提供了公式I的化合物及其药学上可接受的盐和溶剂化物，其中R1、R2、R3、R4、R5、Y、Za如本公开说明所述。本发明还提供了任一公式II至VII、IA至IC和IIA至IIC的化合物及其药学上可接受的盐和溶剂化物。本发明的其他方面包括使用公式I至VII、IA至IC和IIA至IIC的化合物及其药学上可接受的盐和溶剂化物，治疗对一种或多种阿片受体调节敏感的疾病。在某些实施例中，本发明的化合物可用于治疗疼痛。
• 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。