O-Acetylmitragynine hydroxyindolenine | 174418-81-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 柯楠因类生物碱
• 英文名称: O-Acetylmitragynine hydroxyindolenine
• 英文别名: methyl (E)-2-((2S,3S,7aS,12bS)-7a-acetoxy-3-ethyl-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate；7-acetoxymitragynine；methyl (E)-2-[(2S,3S,7aS,12bS)-7a-acetyloxy-3-ethyl-8-methoxy-2,3,4,6,7,12b-hexahydro-1H-indolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate
• CAS: 174418-81-6
• 化学式: C₂₅H₃₂N₂O₆
• 分子量: 456.539
• InChiKey: RJTCCQKAKCMBTR-XBULZMPJSA-N

物化性质

• 沸点：
  571.9±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  86.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  O-Acetylmitragynine hydroxyindolenine 在 sodium hydroxide 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 14.0h， 生成 mitragynine pseudoindoxyl
  参考文献：
  名称：

  Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids:  Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands

  摘要：

  Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid receptors. By utilizing this natural product as a lead compound, synthesis of some derivatives, evaluations of the structure-activity relationship, and surveys of the intrinsic activities and potencies on opioid receptors were performed with guinea pig ileum. The affinities of some compounds for mu-, delta-, and kappa-receptors were determined in a receptor binding assay. The essential structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice.

  DOI：

  10.1021/jm010576e
• 作为产物：
  描述：

  lead(IV) tetraacetate 、 帽柱木碱盐酸盐 以 二氯甲烷 为溶剂， 反应 4.0h， 以31%的产率得到O-Acetylmitragynine hydroxyindolenine
  参考文献：
  名称：

  [EN] MITRAGYNINE ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE LA MITRAGYNINE ET LEURS UTILISATIONS

  摘要：

  本文描述了公式（I'）-（II'）的化合物，公式（I）-（II）的化合物及其药学上可接受的盐。本发明的化合物可用于调节阿片受体活性。所提供的化合物可能对一个或多个阿片受体具有激动和拮抗作用。还描述了使用这些化合物治疗或管理疼痛的方法。

  公开号：

  WO2016176657A1

文献信息

• Formation of an Unusual Dimeric Compound by Lead Tetraacetate Oxidation of a Corynanthe-Type Indole Alkaloid, Mitragynine.
  作者：Hiromitsu Takayama、Hayato Ishikawa、Mariko Kitajima、Norio Aimi

  DOI：10.1248/cpb.50.960

  日期：——

  Lead tetraacetate oxidation of a Corynanthe-type indole alkaloid, mitragynine, produced mainly 7-acetoxyindolenine derivative (2) together with a dimeric compound (4) as a minor product. The novel structure having a bridge between the C-11' and C-7 positions in the respective indolenine parts and its formation mechanism were studied.

  Corynanthe型吲哚生物碱米塔吉宁的四乙酸铅氧化主要生成7-乙酰氧基吲哚烯衍生物（2）和二聚化合物（4）作为副产物。研究了在各个吲哚部分中在C-11′和C-7位置之间具有桥的新颖结构及其形成机理。
• MITRAGYNINE ANALOGS AND USES THEREOF
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US20220024923A1

  公开（公告）日：2022-01-27

  Described herein are compounds of Formulae (I′)-(II′), compounds of Formulae (I)-(II) and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful for modulating opioid receptor activity. The provided compounds may have both agonistic and antagonistic effect on one or more opioid receptors. Methods of using the compounds for treating or managing pain are also described.
• [EN] MITRAGYNINE ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE LA MITRAGYNINE ET LEURS UTILISATIONS
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：WO2016176657A1

  公开（公告）日：2016-11-03

  Described herein are compounds of Formulae (I')-(II'), compounds of Formulae (I)- (II) and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful for modulating opioid receptor activity. The provided compounds may have both agonistic and antagonistic effect on one or more opioid receptors. Methods of using the compounds for treating or managing pain are also described.

  本文描述了公式（I'）-（II'）的化合物，公式（I）-（II）的化合物及其药学上可接受的盐。本发明的化合物可用于调节阿片受体活性。所提供的化合物可能对一个或多个阿片受体具有激动和拮抗作用。还描述了使用这些化合物治疗或管理疼痛的方法。
• Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids:  Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands
  作者：Hiromitsu Takayama、Hayato Ishikawa、Mika Kurihara、Mariko Kitajima、Norio Aimi、Dhavadee Ponglux、Fumi Koyama、Kenjiro Matsumoto、Tomoyuki Moriyama、Leonard T. Yamamoto、Kazuo Watanabe、Toshihiko Murayama、Syunji Horie

  DOI：10.1021/jm010576e

  日期：2002.4.1

  Mitragynine (1) is a major alkaloidal component in the Thai traditional medicinal herb, Mitragyna speciosa, and has been proven to exhibit analgesic activity mediated by opioid receptors. By utilizing this natural product as a lead compound, synthesis of some derivatives, evaluations of the structure-activity relationship, and surveys of the intrinsic activities and potencies on opioid receptors were performed with guinea pig ileum. The affinities of some compounds for mu-, delta-, and kappa-receptors were determined in a receptor binding assay. The essential structural moieties in the Corynanthe type indole alkaloids for inducing the opioid agonistic activity were also clarified. The oxidative derivatives of mitragynine, i.e., mitragynine pseudoindoxyl (2) and 7-hydroxymitragynine (12), were found as opioid agonists with higher potency than morphine in the experiment with guinea pig ileum. In addition, 2 induced an analgesic activity in the tail flick test in mice.