[((4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carbonyl)-amino]-acetic acid methyl ester | 247082-71-9

• 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: [((4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carbonyl)-amino]-acetic acid methyl ester
• CAS: 247082-71-9
• 化学式: C₃₅H₅₅NO₅
• 分子量: 569.825
• InChiKey: VHPOEHXUAFNJCH-XPWYKWPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.01
• 重原子数：
  41.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [((4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carbonyl)-amino]-acetic acid methyl ester 在 sodium acetate 、 乙酸酐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors

  摘要：

  Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular endpoints with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-kappa B, STAT3, Nrf2, TGRS) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (Sb) was selected for further studies, and evaluation of its effect on HIF-la expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.

  DOI：

  10.1021/acs.jnatprod.8b00514
• 作为产物：
  描述：

  齐墩果酸 3-乙酸酯 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 [((4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carbonyl)-amino]-acetic acid methyl ester
  参考文献：
  名称：

  Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors

  摘要：

  Pentacyclic triterpenoid acids (PCTTAs) are pleiotropic agents that target many macromolecular endpoints with low to moderate affinity. To explore the biological space associated with PCTTAs, we have investigated the carboxylate-to-hydroxamate transformation, discovering that it de-emphasizes affinity for the transcription factors targeted by the natural compounds (NF-kappa B, STAT3, Nrf2, TGRS) and selectively induces inhibitory activity on HIF prolyl hydrolases (PHDs). Activity was reversible, isoform-selective, dependent on the hydroxamate location, and negligible when this group was replaced by other chelating elements or O-alkylated. The hydroxamate of betulinic acid (Sb) was selected for further studies, and evaluation of its effect on HIF-la expression under normal and hypoxic conditions qualified it as a promising lead structure for the discovery of new candidates in the realm of neuroprotection.

  DOI：

  10.1021/acs.jnatprod.8b00514

文献信息

• Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
  作者：Yi-Nan Zhang、Wei Zhang、Di Hong、Lei Shi、Qiang Shen、Jing-Ya Li、Jia Li、Li-Hong Hu

  DOI：10.1016/j.bmc.2008.07.080

  日期：2008.9

  Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13

  酪氨酸磷酸酶1B蛋白是胰岛素通路负调节的关键因素，也是治疗糖尿病和肥胖症的有希望的靶标。本文中，通过筛选传统中草药文库中鉴定出的针对PTP1B的天然三萜类化合物齐墩果酸，优化了一系列竞争性抑制剂。在3和28位上进行修饰，我们获得了K（i）为130 nM的化合物13，该化合物在除T细胞蛋白酪氨酸磷酸酶以外的其他与胰岛素途径有关的磷酸酶之间表现出良好的选择性。在细胞模型中的进一步评估表明，这些衍生物增强了CHO / hIR细胞中胰岛素受体的磷酸化作用，并刺激了添加或不添加胰岛素的L6肌管中的葡萄糖摄取。
• Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation
  作者：Yuan Zhang、Jian-xin Li、Jianwei Zhao、Shao-zhong Wang、Yi Pan、Ken Tanaka、Shigetoshi Kadota

  DOI：10.1016/j.bmcl.2005.01.061

  日期：2005.3

  Two series of oleanolic acid derivatives were synthesized and their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) induced by 1 alpha,25-dihydroxy vitamin D-3 was evaluated in a co-culture assay system. The structure-activity relationships, together with electronic structure based on the frontier molecular orbitals, for example, HOMO and LUMO, related to different amino acid substituents were studied. Derivatives with proline or phenylalanine showed a tendency to enhance the inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of potential complement inhibitory semisynthetic analogs of oleanolic acid
  作者：Haregewein Assefa、Alison Nimrod、Larry Walker、Robert Sindelar

  DOI：10.1016/s0960-894x(99)00314-5

  日期：1999.7

  A number of semisynthetic analogs of oleanolic acid have been synthesized and tested for their complement inhibitory, cytotoxic and apoptotic activities. Among these, compounds 10 and 17 exhibited complement inhibitory potency superior to oleanolic acid. Both have also shown a moderate improvement in in vitro therapeutic index (T.I.). (C) 1999 Elsevier Science Ltd. All rights reserved.