butyl (1S,2R,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate | 86166-09-8

• 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: butyl (1S,2R,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate
• 英文别名: butyl (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: 86166-09-8
• 化学式: C₃₄H₅₆O₃
• 分子量: 512.817
• InChiKey: WACYAQNAPIXVBI-GVKTZWNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  正溴丁烷 、 熊果酸 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 以79%的产率得到butyl (1S,2R,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylate
  参考文献：
  名称：

  新型熊果酸衍生物的合成和评价作为潜在的抗肿瘤药

  摘要：

  合成了新的熊果酸衍生物，并通过MS，IR，1 H NMR和13 C NMR光谱分析证实了其结构。通过MTT测定评估了这些化合物对MGC-803（胃癌细胞）和Bcap-37（乳腺癌细胞）人癌细胞系的体外抗肿瘤活性。药理学筛选结果表明，许多衍生物对受试细胞系均表现出中等至高活性，并且大多数药物显示出比熊果酸更强的抑制活性。代表性化合物3h的初步机理研究通过a啶橙/溴化乙锭染色，Hoechst 33258染色，末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记试验以及流式细胞术进行了检测，结果表明化合物3h可以诱导MGC-803细胞凋亡，其凋亡率达到34.59。以10μM处理36小时后的％。

  DOI：

  10.1007/s00044-016-1680-1

文献信息

• Modulators of ROR-gamma Receptors, Composition and Use Thereof
  申请人：KULING THERAPEUTICS

  公开号：US20170298090A1

  公开（公告）日：2017-10-19

  The present invention provides novel methods to treat disease by modulating retinoid-related orphan receptor gamma (ROR-gamma) in vitro and in vivo with ursolic acid analogs, and compositions thereof. The methods and compounds disclosed herein are useful for inhibiting the differentiation of a population of T cells, or treating a disease related to Th17 cell responses in a subject. Examples of such diseases include, but are not limited to, autoimmune diseases, multiple sclerosis, rheumatoid arthritis, psoriasis and diabetes.

  本发明提供了一种通过使用熊果酸类似物在体外和体内调节视黄醇相关孤儿受体γ（ROR-gamma）来治疗疾病的新方法，以及相关组合物。本文披露的方法和化合物对于抑制T细胞群体的分化或治疗与Th17细胞反应相关的疾病非常有用。此类疾病的示例包括但不限于自身免疫疾病、多发性硬化症、类风湿性关节炎、牛皮癣和糖尿病。
• 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.
• In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives
  作者：Jing-Wei Shao、Yong-Chao Dai、Jin-Ping Xue、Ji-Chuang Wang、Feng-Ping Lin、Yang-Hao Guo

  DOI：10.1016/j.ejmech.2011.03.050

  日期：2011.7

  Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 +/- 4.3%) compared to the control group. (C) 2011 Elsevier Masson SAS. All rights reserved.