3β-(benzoyloxy)urs-12-en-28-oic acid | 108650-45-9

• 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-(benzoyloxy)urs-12-en-28-oic acid
• 英文别名: (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-benzoyloxy-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-carboxylic acid
• CAS: 108650-45-9
• 化学式: C₃₇H₅₂O₄
• 分子量: 560.817
• InChiKey: WNBXVNDMCCUPQJ-JKBIDZDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氨基四氮唑 、 3β-(benzoyloxy)urs-12-en-28-oic acid 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以85%的产率得到(3S,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-8a-((1H-tetrazol-5-yl)carbamoyl)-4,4,6a,6b,11,12,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicen-3-yl benzoate
  参考文献：
  名称：

  新型熊果酸四唑衍生物的HIF-1α抑制活性的合成和评价。

  摘要：

  缺氧诱导因子-1α（HIF-1α）通路与肿瘤血管生成，生长和转移有关。因此，抑制该途径是治疗各种类型癌症的重要治疗靶标。在这里，我们设计和合成了31个含有四唑部分的熊果酸（UA）衍生物，并对其作为HIF-1α转录抑制剂的潜在抗肿瘤活性进行了评估。其中，化合物14d（IC50 0.8±0.2 µM）表现出最强的活性，化合物14a（IC50 4.7±0.2 µM）表现出最有前途的生物学特性。对这些化合物与HIF-1α的构效关系的分析表明，位于UA衍生物C-28处的四唑基的存在对其抑制活性至关重要。

  DOI：

  10.1016/j.bmcl.2019.04.028
• 作为产物：
  描述：

  乌索酸苄酯 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 28.0h， 生成 3β-(benzoyloxy)urs-12-en-28-oic acid
  参考文献：
  名称：

  Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors

  摘要：

  Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3 beta-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 mu M in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic tri-terpenoid 3 beta-ester derivatives and CETP protein for the further modification and optimization.

  DOI：

  10.1016/j.bmcl.2019.126824

文献信息

• [EN] COMPOUNDS FOR REDUCING GLUCOCORTICOIDS, AND METHODS OF TREATMENT THEREOF<br/>[FR] COMPOSÉS PERMETTANT DE RÉDUIRE LES GLUCOCORTICOÏDES, ET PROCÉDÉS DE TRAITEMENT ASSOCIÉS
  申请人：BIONICHE LIFE SCIENCES INC

  公开号：WO2014071506A1

  公开（公告）日：2014-05-15

  A method for reducing glucocorticoids in an animal in need thereof comprising the use of compounds of the formula (I), wherein the definitions for R', R1-R11 and n are as disclosed in the description. The compounds of formula (I) are for the treatment or prevention of a glucocorticoid-related disorder for maintaining bone density, maintaining and improving the immune system, treating Cushing' s syndrome, treating obesity, improving reproduction efficiency, treating metabolic disorder, treating hypertension, treating hyperglycemia, treating insulin resistance, treating type 2 diabetes, and/or aiding in cancer and immune therapies

  一种用于减少需要动物体内糖皮质激素的方法，包括使用式(I)的化合物，其中R'、R1-R11和n的定义如描述中所披露。式(I)的化合物用于治疗或预防与糖皮质激素相关的疾病，以维持骨密度、维护和改善免疫系统、治疗库欣综合征、治疗肥胖、提高生殖效率、治疗代谢紊乱、治疗高血压、治疗高血糖、治疗胰岛素抵抗、治疗2型糖尿病，和/或在癌症和免疫疗法中发挥作用。
• Synthesis and Antimicrobial Activity of Ursolic Acid Ester Derivatives
  作者：Vinicius Viana Pereira、Nara Rúbia Pereira、Rafael César Gonçalves Pereira、Lucienir Pains Duarte、Jacqueline Aparecida Takahashi、Roqueline Rodrigues Silva

  DOI：10.1002/cbdv.202100566

  日期：2022.1

  antimicrobial agents. Ursolic acid is a triterpene with known antibacterial action, being naturally found in plants, such as Jaracanda oxyphylla and Jacaranda caroba (Bignoniaceae). Ursolic acid derivative esters have revealed potential biological activities, such as antitumor, antiviral, and antibacterial activity. In this study, sixteen esters (1-16) were synthesized from ursolic acid using DIC/DMAP and characterized

  微生物引起的感染是全世界发病和死亡的主要原因，天然产物仍然是发现新抗菌剂的重要来源。熊果酸是一种具有已知抗菌作用的三萜，天然存在于植物中，例如Jaracanda oxyphylla和Jacaranda caroba （紫葳科）。熊果酸衍生物酯已显示出潜在的生物活性，例如抗肿瘤、抗病毒和抗菌活性。在本研究中，使用 DIC/DMAP 从熊果酸合成了 16 种酯 ( 1 - 16 )，并通过红外 (IR)、核磁共振 ( 1 H- 和13 C-NMR) 和质谱进行了表征。所有熊果酸酯均针对蜡样芽孢杆菌、金黄色葡萄球菌、大肠杆菌、鼠伤寒沙门氏菌和白色念珠菌进行了评估。 6种化合物（ 3、9、11、13、14和16 ）为首次描述，收率高达91.6 %。化合物11 （ 3β- （3,4-二甲氧基苯甲酰基）熊果酸）和15 （ 3β-烟酰熊果酸）显示出良好的抗真菌活性，对白色念珠菌生长的抑制率分别为93.1%和95
• King et al., Journal of the Chemical Society, 1955, p. 4206,4213
  作者：King et al.

  DOI：——

  日期：——
• Synthesis and evaluation of the HIF-1α inhibitory activities of novel ursolic acid tetrazole derivatives
  作者：Lin-Hao Zhang、Zhi-Hong Zhang、Ming-Yue Li、Zhi-Yu Wei、Xue-Jun Jin、Hu-Ri Piao

  DOI：10.1016/j.bmcl.2019.04.028

  日期：2019.6

  metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of cancers. Here, we designed and synthesized 31 ursolic acid (UA) derivatives containing a tetrazole moiety and evaluated them for their potential anti-tumor activities as HIF-1α transcriptional inhibitors. Of these, compound 14d (IC50 0.8 ± 0.2 µM) displayed the most potent activity

  缺氧诱导因子-1α（HIF-1α）通路与肿瘤血管生成，生长和转移有关。因此，抑制该途径是治疗各种类型癌症的重要治疗靶标。在这里，我们设计和合成了31个含有四唑部分的熊果酸（UA）衍生物，并对其作为HIF-1α转录抑制剂的潜在抗肿瘤活性进行了评估。其中，化合物14d（IC50 0.8±0.2 µM）表现出最强的活性，化合物14a（IC50 4.7±0.2 µM）表现出最有前途的生物学特性。对这些化合物与HIF-1α的构效关系的分析表明，位于UA衍生物C-28处的四唑基的存在对其抑制活性至关重要。
• Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors
  作者：Chao Chen、Renhua Sun、Yan Sun、Xuan Chen、Fei Li、Xiaoan Wen、Haoliang Yuan、Dongyin Chen

  DOI：10.1016/j.bmcl.2019.126824

  日期：2020.1

  Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3 beta-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4 mu M in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic tri-terpenoid 3 beta-ester derivatives and CETP protein for the further modification and optimization.