3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid N,N-dimethylamide | 1105067-32-0

• 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 N,N-dimethylamide
• 英文别名: 3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N,N-dimethyl；(2R,4aS,6aS,12bR,14aS,14bR)-10-hydroxy-N,N,2,4a,6a,9,12b,14a-octamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide；(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-N,N,2,4a,6a,6a,9,14a-octamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide
• CAS: 1105067-32-0
• 化学式: C₃₁H₄₃NO₃
• 分子量: 477.687
• InChiKey: RRRZQVJZDVPAJN-ZRCCSVPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  35
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid N,N-dimethylamide 在 甲醇 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  [EN] ANALOGS OF CELASTROL
  [FR] ANALOGUES DE CÉLASTROL

  摘要：

  本文描述了用于治疗或预防肥胖以及使用这些方法的组合物和方法。

  公开号：

  WO2017070615A1
• 作为产物：
  描述：

  雷公藤红素 、 二甲胺 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以67.1%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 N,N-dimethylamide
  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 celastrol derivatives as potential non‐nucleoside hepatitis B virus inhibitors
  作者：He Zhang、Gongxi Lu

  DOI：10.1111/cbdd.13746

  日期：2020.12

  A series of para‐quinone methide (p QM) moiety and C‐20‐ modified derivatives of celastrol were synthesized and evaluated for their inhibitory effect on the secretion of HBsAg and HBeAg as well as the inhibitory effect against HBV DNA replication. The results suggested that amidation of C‐20 carboxylic group could generate derivatives with good anti‐HBV profile, among them compound 14 showed the best

  合成了一系列对醌甲基化物 ( p QM) 部分和 C-20 修饰的 Celastrol 衍生物，并评估了它们对 HBsAg 和 HBeAg 分泌的抑制作用以及对 HBV DNA 复制的抑制作用。结果表明，C-20羧基的酰胺化可以产生具有良好抗HBV特性的衍生物，其中化合物14对HBsAg（IC 50  = 11.9 μ μ）和HBeAg（IC 50  = 13.1 ）的分泌表现出最好的抑制活性µ μ ) 的 SI 分别为 3.3 和 3.0。此外，14还显示出对 HBV DNA 复制的有效抑制作用 (48.5 ± 15.1%, 25 µM)。据我们所知，这是 celastrol 衍生物作为潜在的非核苷 HBV 抑制剂的首次报道。
• CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
  申请人：Qian Xiangping

  公开号：US20120052019A1

  公开（公告）日：2012-03-01

  Chemical entities which are triterpenoid derivatives, pharmaceutical compositions and methods of treatment of inflammatory, neurodegenerative, neoplastic and autoimmune diseases are described.

  本文描述了三萜类衍生物、制药组合物以及治疗炎症、神经退行性、肿瘤和自身免疫性疾病的方法。
• Analogs of celastrol
  申请人：ERX Pharmaceuticals, Inc.

  公开号：US10662218B2

  公开（公告）日：2020-05-26

  Described herein, inter alia, are compositions and methods for treating or preventing obesity and using the same.

  本文特别描述了治疗或预防肥胖症的组合物和方法，以及使用这些组合物和方法的方法。
• Design and synthesis of celastrol derivatives as anticancer agents
  作者：Wen-Jian Tang、Jing Wang、Xu Tong、Jing-Bo Shi、Xin-Hua Liu、Jun Li

  DOI：10.1016/j.ejmech.2015.03.039

  日期：2015.5

  A series of celastrol derivatives as potential telomerase inhibitors were designed and synthesized. The bioassays demonstrated that title compounds displayed potent anticancer activities against SGC-7901, SMMC-7721, MGC-803 and HepG-2 cell lines, among them, compounds 3c and 3d which containing hydrophilicity moieties exhibited high anti-proliferative activities (IC50 = 0.10-1.22 mu M). The preliminary mechanism of antitumor action indicated that title compound 3c could induce significant SMMC-7721 cells apoptosis. A modified TRAP assay showed that compounds 3c and 3d displayed the most potent inhibitory activity with IC50 values at 0.11 and 0.34 mu M, respectively. And there was a good correlation between telomerase inhibition and anti-proliferative inhibition of SMMC-7721 cells. Moreover, molecular docking indicated that the active compound 3c was nicely bound into the telomerase hTERT active site, hydrophobic, van der Waals and two hydrogen bond interactions with conserved residues ASP 628 and TYR 949 were found. (C) 2015 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.