3-methoxy-17-(2,2,2-trichloroethoxycarbonyl)morphinan-6-spiro-2'-(1',3'-dioxolane) | 1357172-85-0

• 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-(2,2,2-trichloroethoxycarbonyl)morphinan-6-spiro-2'-(1',3'-dioxolane)
• CAS: 1357172-85-0
• 化学式: C₂₂H₂₆Cl₃NO₅
• 分子量: 490.811
• InChiKey: JCYGRXKTAVRJME-HQRMLTQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  31.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  57.23
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-methoxy-17-(2,2,2-trichloroethoxycarbonyl)morphinan-6-spiro-2'-(1',3'-dioxolane) 在 水 、 三乙酰氧基硼氢化钠 、 potassium hydroxide 作用下， 以 二氯甲烷 、 二甲基亚砜 、 异丙醇 为溶剂， 反应 9.0h， 生成 3-methoxy-17-phenethylmorphinan-6-spiro-2'-(1',3'-dioxolane)
  参考文献：
  名称：

  Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.11.047
• 作为产物：
  描述：

  (1'R,9'R,10'S)-17'-(cyclopropylmethyl)-4'-methoxyspiro[1,3-dioxolane-2,13'-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene]-10'-ol 在 吡啶 、 platinum(IV) oxide 、 氯化亚砜 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 1,1,2,2-四氯乙烷 为溶剂， 反应 24.0h， 生成 3-methoxy-17-(2,2,2-trichloroethoxycarbonyl)morphinan-6-spiro-2'-(1',3'-dioxolane)
  参考文献：
  名称：

  Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.11.047

文献信息

• Essential structure of orexin 1 receptor antagonist YNT-707, part III: Role of the 14-hydroxy and the 3-methoxy groups in antagonistic activity toward the orexin 1 receptor in YNT-707 derivatives lacking the 4,5-epoxy ring
  作者：Naoshi Yamamoto、Sayaka Ohrui、Takahiro Okada、Tsuyoshi Saitoh、Noriki Kutsumura、Yasuyuki Nagumo、Yoko Irukayama-Tomobe、Yasuhiro Ogawa、Yukiko Ishikawa、Yurie Watanabe、Daichi Hayakawa、Hiroaki Gouda、Masashi Yanagisawa、Hiroshi Nagase

  DOI：10.1016/j.bmc.2019.03.010

  日期：2019.4

  Morphinan derivatives lacking the 4,5-epoxy ring were synthesized to examine the participation of the 14-OH group, the 3-OMe group, and the aromaticity of the A-ring in the activity and selectivity for the orexin 1 receptor (OX1R). The assay results and the conformational analyses of the 14-dehydrated and 14-H derivatives suggested that the orientations of the 6-amide side chain and the 17-benzenesulfonyl

  合成缺乏4,5-环氧环的吗啡衍生物，以检查14-OH，3-OMe基团和A环的芳香性对orexin 1受体（OX1R）的活性和选择性的参与。14个脱水和14-H衍生物的分析结果和构象分析表明，6-酰胺侧链和17-苯磺酰基的取向将在OX1R的活性中起重要作用。在6β衍生物中，3-OMe基团的去除和A环的减少显着降低了对OX1R的活性，但这些变化并未影响6α衍生物。这些结果表明3-OMe基团和A-环将是6β-衍生物必不可少的结构部分。