(4aS,6aR,6bS,8aR,12aS,14bS)-Methyl 11-cyano-2,2,6a,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-4a-carboxylate | 218600-53-4

• 物质功能分类: 生物化工 - 抑制剂 - 核转录因子(NF-κB)
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4aS,6aR,6bS,8aR,12aS,14bS)-Methyl 11-cyano-2,2,6a,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-4a-carboxylate
• 英文别名: methyl (4aS,6aR,6bS,8aR,12aS,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylate
• CAS: 218600-53-4
• 化学式: C₃₂H₄₃NO₄
• 分子量: 505.7
• InChiKey: WPTTVJLTNAWYAO-FUARBKCBSA-N

物化性质

• 熔点：
  215-223°C
• 沸点：
  600.8±55.0 °C(Predicted)
• 密度：
  1.15
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  37
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  84.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险品运输编号：
  NONH for all modes of transport
• 海关编码：
  2926909090
• WGK Germany：
  3

制备方法与用途

生物活性

Bardoxolone Methyl（RTA 402, TP-155, NSC 713200, CDDO Methyl Ester, CDDO-Me）是一种IKK抑制剂，具有强烈的促凋亡和抗炎作用。同时它还是有效的Nrf2激活剂和NF-κB抑制剂，并能抑制铁死亡。在癌细胞中，Bardoxolone Methyl可诱导凋亡和自噬。

靶点

Target	Value
IKK	(Cell-free assay)
Ferroptosis	()
Nrf2	()
NF-κB	()

体外研究

Bardoxolone Methyl作用于小鼠巨噬细胞，对interferon-Ƴ诱导的一氧化氮的产生具有强效抑制活性，其IC50为0.1 nM。它降低白血病HL-60、KG-1和NB4细胞的生存能力，IC50分别为0.4 μM、0.4 μM 和 0.27 μM。CDDO-ME诱导促凋亡Bax蛋白表达，抑制ERK1 / 2的活化，并且它抑制Bcl-2的磷酸化，这有助于诱导细胞凋亡。此外，Bardoxolone Methyl能有效地抑制由(IL)-1beta、phorbol ester、okadaic acid、hydrogen peroxide、lipopolysaccharide和cigarette smoke激活的组成型和可诱导的NF-κB的肿瘤坏死因子。

体内研究

在动物实验中，Bardoxolone Methyl（60 mg/kg）能减少肺肿瘤的数量、大小及严重程度。它还能显著降低LPS刺激下的体内炎症反应，并通过诱导脾脏HO-1蛋白表达来对抗致死剂量的LPS对小鼠的毒性。

用途

CDDO Methyl Ester是一种合成三萜类化合物，可通过下调核因子κB调节的基因产物在人类白血病细胞中抑制I κBα激酶并增强由TNF和化疗药物诱导的凋亡。它是一种治疗急性髓性白血病和胰腺癌的新疗法，并且也可用于其他形式癌症的治疗。

反应信息

• 作为反应物：
  描述：

  (4aS,6aR,6bS,8aR,12aS,14bS)-Methyl 11-cyano-2,2,6a,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-4a-carboxylate 在 lithium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以96 %的产率得到(4aS,6aR,6bS,8aR,12aS,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylic acid
  参考文献：
  名称：

  CHEMICAL SYNTHESIS METHODS AND CDDO/CDDO-EA PREPARATIONS

  摘要：

  Improved synthesis methods for providing a Compound #6, Compound #7 and various CDDO, CDDO derivatives and CDDO analogs, are provided. Product compositions comprising CDDO, CDDO-EA, CDDO-Me prepared according to the methods disclosed are also provided. Synthesis methods taking less than about 12 hours, or less than about 2 hours, that are scalable and provide commercially useful and economically suitable yield CDDO compound products are disclosed.

  公开号：

  WO2024145527A1
• 作为产物：
  描述：

  齐墩果酸 在 氟苯 、 potassium carbonate 、 间氯过氧苯甲酸 、 potassium iodide 、 2-碘酰基苯甲酸 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.5h， 生成 (4aS,6aR,6bS,8aR,12aS,14bS)-Methyl 11-cyano-2,2,6a,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-4a-carboxylate
  参考文献：
  名称：

  CHEMICAL SYNTHESIS METHODS AND CDDO/CDDO-EA PREPARATIONS

  摘要：

  Improved synthesis methods for providing a Compound #6, Compound #7 and various CDDO, CDDO derivatives and CDDO analogs, are provided. Product compositions comprising CDDO, CDDO-EA, CDDO-Me prepared according to the methods disclosed are also provided. Synthesis methods taking less than about 12 hours, or less than about 2 hours, that are scalable and provide commercially useful and economically suitable yield CDDO compound products are disclosed.

  公开号：

  WO2024145527A1

文献信息

• [EN] USE OF TRITERPENOID NRF2 INHIBITORS<br/>[FR] UTILISATION D'INHIBITEURS DE NRF2 TRITERPÉNOÏDES
  申请人：FRONTHERA U S PHARMACEUTICALS LLC

  公开号：WO2021202720A1

  公开（公告）日：2021-10-07

  Described herein are terpinoid derivatives as NRF2 inhibitors for use in treating systemic lupus nephritis, diabetic chronic kidney disease (CDK), Alport syndrome, focal segmental glomerulosclerosis (FSGS), pulmonary hypertension, Friedreich's ataxia, autosomal dominant polycystic kidney disease (ADPKD), or IgA nephropathy.
• CHEMICAL SYNTHESIS METHODS AND CDDO/CDDO-EA PREPARATIONS
  申请人：[en]THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：WO2024145527A1

  公开（公告）日：2024-07-04

  Improved synthesis methods for providing a Compound #6, Compound #7 and various CDDO, CDDO derivatives and CDDO analogs, are provided. Product compositions comprising CDDO, CDDO-EA, CDDO-Me prepared according to the methods disclosed are also provided. Synthesis methods taking less than about 12 hours, or less than about 2 hours, that are scalable and provide commercially useful and economically suitable yield CDDO compound products are disclosed.