tert-butoxycarbonylmethyl 3β-hydroxyurs-12-en-28-oate | 1198208-29-5

• 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: tert-butoxycarbonylmethyl 3β-hydroxyurs-12-en-28-oate
• 英文别名: [2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl] (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylate
• CAS: 1198208-29-5
• 化学式: C₃₆H₅₈O₅
• 分子量: 570.854
• InChiKey: NZHQIWKYMQURQU-SQXVXACQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butoxycarbonylmethyl 3β-hydroxyurs-12-en-28-oate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以64.3%的产率得到carboxymethyl 3β-hydroxyurs-12-en-28-oate
  参考文献：
  名称：

  SENP1抑制剂熊果酸衍生物的发现及放射增敏研究

  摘要：

  SUMO化和去SUMO化在DNA损伤反应和放疗抵抗的形成中发挥着重要作用。 SENP1是催化去SUMO化修饰的主要特异性异肽酶。抑制 SENP1 会上调癌细胞的放射敏感性，使其成为放射增敏的有希望的靶标。在此，基于熊果酸（UA）的结构，总共设计并合成了53个五环三萜衍生物作为SENP1抑制剂。十种衍生物表现出比UA更好的SENP1抑制活性，并讨论了初步的构效关系。大多数UA衍生物的细胞毒性较低，其中化合物36的放射增敏活性最好， SER值为1.45。这是第一项开发小分子 SENP1 抑制剂作为放射增敏剂的研究。

  DOI：

  10.1016/j.ejmech.2021.113918
• 作为产物：
  描述：

  溴乙酸叔丁酯 、 熊果酸 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97.2%的产率得到tert-butoxycarbonylmethyl 3β-hydroxyurs-12-en-28-oate
  参考文献：
  名称：

  SENP1抑制剂熊果酸衍生物的发现及放射增敏研究

  摘要：

  SUMO化和去SUMO化在DNA损伤反应和放疗抵抗的形成中发挥着重要作用。 SENP1是催化去SUMO化修饰的主要特异性异肽酶。抑制 SENP1 会上调癌细胞的放射敏感性，使其成为放射增敏的有希望的靶标。在此，基于熊果酸（UA）的结构，总共设计并合成了53个五环三萜衍生物作为SENP1抑制剂。十种衍生物表现出比UA更好的SENP1抑制活性，并讨论了初步的构效关系。大多数UA衍生物的细胞毒性较低，其中化合物36的放射增敏活性最好， SER值为1.45。这是第一项开发小分子 SENP1 抑制剂作为放射增敏剂的研究。

  DOI：

  10.1016/j.ejmech.2021.113918

文献信息

• URSOLIC ACID DERIVATIVE AND PHARMACEUTICAL COMPOSITION THEREOF
  申请人：Lin Chun-Nan

  公开号：US20110190388A1

  公开（公告）日：2011-08-04

  Several ursolic acid derivatives and pharmaceutical compositions thereof are provided. The ursolic acid derivatives and the pharmaceutical compositions thereof have at least one of an anticancer and an anti-inflammatory effects. A method for increasing a reactive oxygen species in a cell is also provided. The method comprises a step of providing the cell with a pharmaceutical composition including an ursolic acid derivative.

  提供了几种熊果酸衍生物及其药物组合物。这些熊果酸衍生物和药物组合物具有抗癌和抗炎作用中的至少一种。还提供了一种增加细胞中活性氧自由基的方法。该方法包括向细胞提供包含熊果酸衍生物的药物组合物的步骤。
• Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species
  作者：Huang-Yao Tu、A-Mei Huang、Bai-Luh Wei、Kim-Hong Gan、Tzyh-Chyuan Hour、Shyh-Chyun Yang、Yeong-Shiau Pu、Chun-Nan Lin

  DOI：10.1016/j.bmc.2009.08.046

  日期：2009.10

  Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 mu M) and 23 (20 and 50 mu M) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 mu M) and 23 (20 and 50 mu M) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h. (C) 2009 Elsevier Ltd. All rights reserved.
• US8729055B2
  申请人：——

  公开号：US8729055B2

  公开（公告）日：2014-05-20
• Discovery and radiosensitization research of ursolic acid derivatives as SENP1 inhibitors
  作者：Huiqiang Wei、Jianghong Guo、Xiao Sun、Wenfeng Gou、Hongxin Ning、Zhennan Fang、Qiang Liu、Wenbin Hou、Yiliang Li

  DOI：10.1016/j.ejmech.2021.113918

  日期：2022.1

  specific isopeptidase to catalyze deSUMOylation modification. Inhibiting SENP1 upregulates cancer cell radiosensitivity and it becomes a promising target for radiosensitization. Herein, based on the structure of ursolic acid (UA), a total of 53 pentacyclic triterpene derivatives were designed and synthesized as SENP1 inhibitors. Ten derivatives exhibited better SENP1 inhibitory activities than UA and the

  SUMO化和去SUMO化在DNA损伤反应和放疗抵抗的形成中发挥着重要作用。 SENP1是催化去SUMO化修饰的主要特异性异肽酶。抑制 SENP1 会上调癌细胞的放射敏感性，使其成为放射增敏的有希望的靶标。在此，基于熊果酸（UA）的结构，总共设计并合成了53个五环三萜衍生物作为SENP1抑制剂。十种衍生物表现出比UA更好的SENP1抑制活性，并讨论了初步的构效关系。大多数UA衍生物的细胞毒性较低，其中化合物36的放射增敏活性最好， SER值为1.45。这是第一项开发小分子 SENP1 抑制剂作为放射增敏剂的研究。