3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid isopropyl ester | 1105067-40-0

• 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: 3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid isopropyl ester
• 英文别名: (9β,13α,14β,20α)-3-hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid 1-methylethyl ester；propan-2-yl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate
• CAS: 1105067-40-0
• 化学式: C₃₂H₄₄O₄
• 分子量: 492.699
• InChiKey: RPGDRWMPFKEMPI-JSJVQHDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-碘代丙烷 、 雷公藤红素 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以77.6%的产率得到3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid isopropyl ester
  参考文献：
  名称：

  作为具有改善的类药物性质的Hsp90-Cdc37相互作用干扰物的天青衍生物的优化和生物学评估

  摘要：

  在过去的十年中，作为肿瘤治疗分子靶标的热休克蛋白90（Hsp90）引起了人们的极大关注。Hsp90多分子伴侣复合物在癌细胞的生长和/或存活中具有重要作用。Cdc37，作为伴侣蛋白，将激酶客户与Hsp90相关联，并促进恶性肿瘤的发展。破坏Hsp90-Cdc37的相互作用提供了一种抑制Hsp90在癌症治疗中功能的替代策略。Celastrol，作为天然产物，可以破坏Hsp90-Cdc37的相互作用并诱导激酶客户的降解。此处进行的研究试图阐明作为Hsp90–Cdc37干扰物的Celastrol衍生物的结构与活性之间的关系，并改善类似药物的性质。设计，合成了23种天甾醇衍生物，并测定其生物学活性和理化性质。导数CEL20显示出改善的Hsp90–Cdc37破坏活性，抗增殖活性以及类似药物的特性。此外，CEL20诱导Panc-1细胞中的客体降解，细胞周期停滞和凋亡。这项研究可为发现新型Hsp90–Cdc37干扰物提供参考。

  DOI：

  10.1016/j.bmc.2016.08.070

文献信息

• Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities
  作者：Wei-Guang Shan、Han-Guang Wang、Yan Chen、Rui Wu、Yan-Tao Wen、Li-Wen Zhang、You-Min Ying、Jian-Wei Wang、Zha-Jun Zhan

  DOI：10.1016/j.bmcl.2017.05.083

  日期：2017.8

  A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1–26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not

  设计并合成了一系列3-氨基甲酸酯和29％的Celastrol衍生物（化合物1至26）。评估了这些类似物对几种癌细胞系的细胞毒活性。细胞毒性数据表明，取代基的性质和取代位置对细胞毒活性具有重要影响。用尺寸受限的基团修饰C-3羟基并没有明显降低活性。像哌嗪这样的极性基团的引入可以提高溶解度。选择化合物23以进一步评估体内抗肿瘤功效。在体内显示出比Celastrol更高的抑制率和更好的安全性通过胃内给药进行实验。体内化合物23 的初步抗肿瘤研究表明，它对于开发新的抗肿瘤药物可能很有希望。
• SAR study of celastrol analogs targeting Nur77-mediated inflammatory pathway
  作者：Ziwen Chen、Duo Zhang、Siwei Yan、Chaochao Hu、Zhenfei Huang、Zhuoer Li、Shuangzhou Peng、Xiaotong Li、Yi Zhu、Hongyu Yu、Baohuan Lian、Qi Kang、Mingyu Li、Zhiping Zeng、Xiao-Kun Zhang、Ying Su

  DOI：10.1016/j.ejmech.2019.05.009

  日期：2019.9

  Nur77, an orphan member of the nuclear receptor superfamily, plays an important role in the regulation of inflammatory processes. Our previous work found that celastrol, a pentacyclic triterpene, bound to Nur77 to inhibit inflammation in a Nur77-dependent manner. Celastrol binding to Nur77 promotes Nur77 translocation from nucleus to cytoplasm, resulting in clearance of inflamed mitochondria and then alleviation of inflammation. Here, we report the design, synthesis, SAR study and biological evaluation of a series of celastrol analogs. A total of 24 celastrol derivatives were made. Compound 3a with a K-d of 0.87 mu M was found to be less toxic than celastrol and could be a hit molecule for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.
• COMPOSITIONS AND METHODS FOR INHIBITING GROWTH AND METASTASIS OF MELANOMA
  申请人：Ronai Ze'ev A.

  公开号：US20090054438A1

  公开（公告）日：2009-02-26

  There are provided methods of inhibiting growth and metastasis of melanoma, methods of sensitizing melanoma cells to apoptosis, and methods of treating a subject having melanoma using acetyl isogambogic acid, celastrol, or a derivative thereof. There are further provided derivatives of celastrol and compositions comprising acetyl isogambogic acid, celastrol, or a derivative thereof.
• Compositions and Methods for Inhibiting Growth and Metastasis of Melanoma
  申请人：Ronai Ze'ev A.

  公开号：US20110166216A1

  公开（公告）日：2011-07-07

  There are provided methods of inhibiting growth and metastasis of melanoma, methods of sensitizing melanoma cells to apoptosis, and methods of treating a subject having melanoma using acetyl isogambogic acid, celastrol, or a derivative thereof. There are further provided derivatives of celastrol and compositions comprising acetyl isogambogic acid, celastrol, or a derivative thereof.
• US7776894B2
  申请人：——

  公开号：US7776894B2

  公开（公告）日：2010-08-17