3β-[(2-carboxyphenyl)carbonyloxy]-olean-12-en-28-oic acid | 4847-31-8

• 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: 3β-[(2-carboxyphenyl)carbonyloxy]-olean-12-en-28-oic acid
• 英文别名: 3-β-(2-carboxybenzoyloxy)oleanolic acid；3-(2-carboxybenzoyloxy)-oleanolic acid；(4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-(2-carboxybenzoyloxy)-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(2-carboxybenzoyl)oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
• CAS: 4847-31-8
• 化学式: C₃₈H₅₂O₆
• 分子量: 604.827
• InChiKey: XJBAFGLYCZZECZ-HZGSLRQESA-N

物化性质

• 熔点：
  166-168 °C
• 沸点：
  697.1±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  苯酐 、 齐墩果酸 在 吡啶 、 4-二甲氨基吡啶 作用下， 以75%的产率得到3β-[(2-carboxyphenyl)carbonyloxy]-olean-12-en-28-oic acid
  参考文献：
  名称：

  五环三萜3β-酯衍生物作为新型胆固醇酯转移蛋白抑制剂的发现

  摘要：

  设计，合成和评估了一系列五环三萜3β-酯衍生物，将其作为治疗血脂异常的一类新的胆固醇酯转移蛋白（CETP）抑制剂。体外筛选试验表明，30种化合物中有5种显示出适度的抑制人CETP活性，IC 50小于10μM。其中，化合物20（IC 50  = 2.3μM）具有最强的生物学活性，可有效改善人脂肪组织特异性CETP转基因（ap2-CETPTg）小鼠和豚鼠的血浆脂质水平。额外的安全性评估（豚鼠没有血压升高）和药代动力学研究表明，化合物20的潜在可药性 这是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。

  DOI：

  10.1016/j.ejmech.2017.08.012

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。
• 2-SUBSTITUTED OLEANOLIC ACID DERIVATIVE, METHOD PREPARING FOR SAME, AND APPLICATION THEREOF
  申请人：Hangzhou Bensheng Pharmaceutical Co., Ltd.

  公开号：EP2786757A1

  公开（公告）日：2014-10-08

  The present invention belongs to the field of natural medicine and pharmaceutical chemistry, and specifically relates to novel 2-substituted oleanolic acid derivatives of formula (I) or a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments.

  本发明属于天然药物和药物化学领域，具体涉及式（I）的新型 2-取代齐墩果酸衍生物或其药学上可接受的盐、制备这些化合物的工艺、含有这些化合物的组合物及其在制备抗肿瘤药物中的用途。
• Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents
  作者：Andres Parra、Samuel Martin-Fonseca、Francisco Rivas、Fernando J. Reyes-Zurita、Marta Medina-O'Donnell、Antonio Martinez、Andres Garcia-Granados、Jose A. Lupiañez、Fernando Albericio

  DOI：10.1016/j.ejmech.2013.12.049

  日期：2014.3

  A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the bl6f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC50 values between 0.31 and 15.6 mu M, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.
• OLEANOLIC ACID AMIDATE DERIVATIVES, PREPARATION METHODS AND USES THEREOF
  申请人：Hangzhou Bensheng Pharmaceutical Co., Ltd.

  公开号：EP2787002B1

  公开（公告）日：2016-06-01
• EP2786757B1
  申请人：——

  公开号：EP2786757B1

  公开（公告）日：2017-08-16