((2S,3aR,3bS,6aR,9aR,9bR,10R,11aR)-2-benzyl-6a-hydroxy-8,10-dimethyl-7-oxo-11a-(prop-1-en-2-yl)-3a,3b,6,6a,9a,10,11,11a-octahydro-7H-2,9b-epoxyazuleno[5',4':3,4]benzo[1,2-d][1,3]dioxol-5-yl)methyl 2-(2,3-difluorophenyl)acetate | 1134165-03-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ((2S,3aR,3bS,6aR,9aR,9bR,10R,11aR)-2-benzyl-6a-hydroxy-8,10-dimethyl-7-oxo-11a-(prop-1-en-2-yl)-3a,3b,6,6a,9a,10,11,11a-octahydro-7H-2,9b-epoxyazuleno[5',4':3,4]benzo[1,2-d][1,3]dioxol-5-yl)methyl 2-(2,3-difluorophenyl)acetate
• CAS: 1134165-03-9
• 化学式: C₃₆H₃₆F₂O₇
• 分子量: 618.674
• InChiKey: PKOQUWOJZXCNKH-TUUCAGGVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  45.0
• 可旋转键数：
  7.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  91.29
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2,3-二氟苯乙酸 、 6,7-去环氧-6,7-二去氢-5-脱氧-21-去苯基-21-(苯基甲基)瑞香毒素 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以92%的产率得到((2S,3aR,3bS,6aR,9aR,9bR,10R,11aR)-2-benzyl-6a-hydroxy-8,10-dimethyl-7-oxo-11a-(prop-1-en-2-yl)-3a,3b,6,6a,9a,10,11,11a-octahydro-7H-2,9b-epoxyazuleno[5',4':3,4]benzo[1,2-d][1,3]dioxol-5-yl)methyl 2-(2,3-difluorophenyl)acetate
  参考文献：
  名称：

  Non-vanillyl resiniferatoxin analogues as potent and metabolically stable transient receptor potential vanilloid 1 agonists

  摘要：

  A series of non-vanillyl resiniferatoxin analogues, having 4-methylsulfonylaminophenyl and fluorophenyl moieties as vanillyl surrogates, have been investigated as ligands for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Although lacking the metabolically problematic 4-hydroxy substituent on the A-region phenyl ring, the compounds retained substantial agonist potency. Indeed, the 3-methoxy-4-methylsulfonylaminophenyl analog (1) was modestly (2.5-fold) more potent than RTX, with an EC50 = 0.106 nM. Further, it resembled RTX in its kinetics and pattern of stimulation of the levels of intracellular calcium in individual cells, as revealed by imaging. Compound 1 displayed modestly enhanced in vitro stability in rat liver microsomes and in plasma, suggesting that it might be a pharmacokinetically more favorable surrogate of resiniferatoxin. Molecular modeling analyses with selected analogues provide evidence that the conformational differences could affect their binding affinities, especially for the ester versus amide at the B-region. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.085