(2S,4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-2-carboxylic acid | 1301253-53-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-2-carboxylic acid
• 英文别名: soloxolone；(2S,4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-2-carboxylic acid
• CAS: 1301253-53-1
• 化学式: C₃₁H₄₁NO₄
• 分子量: 491.671
• InChiKey: AVAFUDKPSJHQEM-MEZFCMJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.29
• 重原子数：
  36.0
• 可旋转键数：
  1.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  95.23
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S,4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-2-carboxylic acid 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (4aR,6aS,6bR,8aS,11S,12aS,12bR,14bS)-11-(5-amino-1,3,4-oxadiazol-2-yl)-4,4,6a,6b,8a,11,14b-heptamethyl-3,13-dioxo-3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-2-carbonitrile
  参考文献：
  名称：

  WO2020068689A5

  摘要：

  公开号：

  WO2020068689A5
• 作为产物：
  描述：

  甘草次酸 在 吡啶 、 盐酸 、 甲醇 、 Jones reagent 、 硫酸 、 zinc amalgam 、 盐酸羟胺 、 氢溴酸 、 双氧水 、 溴 、 sodium methylate 、 sodium acetate 、 乙酸酐 、 sodium hydride 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 potassium hydroxide 、 lithium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 71.92h， 生成 (2S,4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,4a,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-2-carboxylic acid
  参考文献：
  名称：

  Synthesis of methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate analogues to determine the active groups for inhibiting cell growth and inducing apoptosis in leukemia cells

  摘要：

  合成了14种具有不同C环结构的2-氰基-3,12-二氧-18β-油烯-1,9(11)-二烯-30-酸甲酯(CDODO-Me-12，10d)类似物，以确定抑制人白血病HL-60细胞增殖和诱导凋亡的活性基团。C环中需要一个不饱和基团来维持抑制细胞增殖和诱导凋亡的能力。C环中具有9(11),12-二烯的化合物10e显示出了与10d相当的诱导凋亡能力，这与其降低了c-FLIP而非Mcl-1和XIAP的水平有关。与化合物10d相比，化合物10e的耗竭谷胱甘肽能力降低。化合物10e是一种通过不同于化合物10d的作用机制发挥活性的新型活性化合物。

  DOI：

  10.1039/c4ob00703d

文献信息

• GLYCYRRHETINIC ACID DERIVATIVES AND METHODS OF USE THEREOF
  申请人：AbbVie Inc.

  公开号：US20140073700A1

  公开（公告）日：2014-03-13

  The present application relates to: (a) compounds of Formula (I): and salts thereof, wherein Y and Z are as defined in the specification; (b) compositions comprising such compounds and salts; and (c) methods of use of such compounds, salts, and compositions, particularly use for the treatment and prevention of diseases such as those associated with oxidative stress and inflammation.

  本申请涉及以下内容：(a) 公式(I)化合物及其盐，其中Y和Z如规范中定义；(b) 包含此类化合物和盐的组合物；以及(c) 使用此类化合物、盐和组合物的方法，尤其用于治疗和预防与氧化应激和炎症相关的疾病。
• Novel Soloxolone Amides as Potent Anti-Glioblastoma Candidates: Design, Synthesis, In Silico Analysis and Biological Activities In Vitro and In Vivo
  作者：Andrey V. Markov、Anna A. Ilyina、Oksana V. Salomatina、Aleksandra V. Sen’kova、Alina A. Okhina、Artem D. Rogachev、Nariman F. Salakhutdinov、Marina A. Zenkova

  DOI：10.3390/ph15050603

  日期：——

  The modification of natural or semisynthetic triterpenoids with amines can be explored as a promising strategy for improving their pharmacological properties. Here, we report the design and synthesis of 11 novel amide derivatives of soloxolone methyl (SM), a cyano enone-bearing derivative of 18βH-glycyrrhetinic acid. Analysis of their bioactivities in vitro and in silico revealed their high toxicity against a panel of tumor cells (average IC50(24h) = 3.7 µM) and showed that the formation of amide moieties at the C-30 position of soloxolone did not enhance the cytotoxicity of derivatives toward tumor cells compared to SM, though it can impart an ability to pass across the blood–brain barrier. Further HPLC–MS/MS and mechanistic studies verified significant brain accumulation of hit compound 12 (soloxolone tryptamide) in a murine model and showed its high anti-glioblastoma potential. It was found that 12 induced ROS-dependent and autophagy-independent death of U87 and U118 glioblastoma cells via mitochondrial apoptosis and effectively blocked their clonogenicity, motility and capacity to form vessel-like structures. Further in vivo study demonstrated that intraperitoneal injection of 12 at a dosage of 20 mg/kg effectively inhibited the growth of U87 glioblastoma in a mouse xenograft model, reducing the proliferative potential of the tumor and leading to a depletion of collagen content and normalization of blood vessels in tumor tissue. The obtained results clearly demonstrate that 12 can be considered as a promising leading compound for drug development in glioblastoma treatment.

  天然或半合成三萜类物质与胺类的修饰可以作为改善其药理学性质的有前途的策略。在这里，我们报道了11种新型苏洛酮甲基（SM）酰胺衍生物的设计和合成，这是一种含有氰基烯酮的18βH-甘草酸衍生物。体外和体内模拟分析表明，它们对一系列肿瘤细胞具有高毒性（平均IC50（24小时）= 3.7μM），并且显示在苏洛酮的C-30位置形成酰胺基团不会增强衍生物对肿瘤细胞的细胞毒性，尽管它可以赋予其穿越血脑屏障的能力。进一步的HPLC-MS/MS和机制研究验证了命中化合物12（苏洛酮色胺）在小鼠模型中的显著脑积累，并显示其高抗胶质母细胞瘤潜力。发现12通过线粒体凋亡诱导ROS依赖性和自噬无关性死亡U87和U118胶质母细胞瘤细胞，并有效阻止了它们的克隆形成能力、运动性和形成血管样结构的能力。进一步的体内研究表明，腹腔注射12剂量为20 mg/kg可以有效抑制小鼠异种移植模型中U87胶质母细胞瘤的生长，减少肿瘤的增殖潜力，并导致肿瘤组织中胶原含量的耗竭和血管的正常化。所得结果清楚地表明12可以被视为胶质母细胞瘤治疗药物开发的有前途的领先化合物。
• Protective effect of soloxolone derivatives in carrageenan- and LPS-driven acute inflammation: Pharmacological profiling and their effects on key inflammation-related processes
  作者：Aleksandra V. Sen’kova、Innokenty A. Savin、Kirill V. Odarenko、Oksana V. Salomatina、Nariman F. Salakhutdinov、Marina A. Zenkova、Andrey V. Markov

  DOI：10.1016/j.biopha.2023.114231

  日期：2023.3
• GLYCYRRHETINIC ACID DERIVATIVES WITH ANTI-INFLAMMATORY ACTIVITY
  申请人：AbbVie Inc.

  公开号：EP2892910B1

  公开（公告）日：2016-09-07
• TERPINOID DERIVATIVES AND USES THEREOF
  申请人：SICHUAN HAISCO PHARMACEUTICAL CO., LTD.

  公开号：US20220017566A1

  公开（公告）日：2022-01-20

  Described herein are terpinoid derivatives as NRF2 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of inflammatory diseases.