(1R,2S,5S,8R,9S,10S,14R,15R,23R)-1,2,8,9,15,22,22-heptamethyl-N-(4-nitrophenyl)-20-oxa-19-azahexacyclo[12.11.0.02,11.05,10.015,23.017,21]pentacosa-11,17(21),18-triene-5-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1R,2S,5S,8R,9S,10S,14R,15R,23R)-1,2,8,9,15,22,22-heptamethyl-N-(4-nitrophenyl)-20-oxa-19-azahexacyclo[12.11.0.02,11.05,10.015,23.017,21]pentacosa-11,17(21),18-triene-5-carboxamide
• 化学式: C₃₇H₄₉N₃O₄
• 分子量: 599.814
• InChiKey: SLGOGCKNPNWOKB-IDSDQTAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  44
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氧代-12-烯-28-乌苏酸 在 草酰氯 、 盐酸羟胺 、 sodium methylate 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 62.0h， 生成 (1R,2S,5S,8R,9S,10S,14R,15R,23R)-1,2,8,9,15,22,22-heptamethyl-N-(4-nitrophenyl)-20-oxa-19-azahexacyclo[12.11.0.02,11.05,10.015,23.017,21]pentacosa-11,17(21),18-triene-5-carboxamide
  参考文献：
  名称：

  Ursolic acid derivatives as bone anabolic agents targeted to tryptophan hydroxylase 1 (Tph-1)

  摘要：

  Tryptophan hydroxylase 1 (Tph-1) initiates the biosynthesis of peripheral serotonin. As peripheral serotonin suppresses bone formation, inhibitor of Tph-1 provides a useful tool to discover anabolic agents for osteoporosis. In the present study, series of ursolic acid (UA) derivatives were synthesized, and their inhibitory activity on serotonin biosynthesis and cytotoxicity were evaluated. Among the derivatives, 8d with potent inhibitory activity on serotonin was applied for further research. The data revealed that 8d significantly inhibited protein and mRNA expressions of Tph-1, and an SPR study indicated that 8d directly interacted to Tph-1 with a binding affinity of KD=15.09μM. Oral administration of 8d significantly prevented bone loss via suppressing serotonin biosynthesis without estrogenic side-effects in ovariectomized (OVX) rats.

  DOI：

  10.1016/j.ejps.2015.04.021

文献信息

• Ursolic acid derivatives as bone anabolic agents targeted to tryptophan hydroxylase 1 (Tph-1)
  作者：Hai-Jian Fu、Yang Zhao、Yu-Ren Zhou、Bei-Hua Bao、Yun Du、Jian-Xin Li

  DOI：10.1016/j.ejps.2015.04.021

  日期：2015.8

  Tryptophan hydroxylase 1 (Tph-1) initiates the biosynthesis of peripheral serotonin. As peripheral serotonin suppresses bone formation, inhibitor of Tph-1 provides a useful tool to discover anabolic agents for osteoporosis. In the present study, series of ursolic acid (UA) derivatives were synthesized, and their inhibitory activity on serotonin biosynthesis and cytotoxicity were evaluated. Among the derivatives, 8d with potent inhibitory activity on serotonin was applied for further research. The data revealed that 8d significantly inhibited protein and mRNA expressions of Tph-1, and an SPR study indicated that 8d directly interacted to Tph-1 with a binding affinity of KD=15.09μM. Oral administration of 8d significantly prevented bone loss via suppressing serotonin biosynthesis without estrogenic side-effects in ovariectomized (OVX) rats.