(4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicen-4a-carboxamide | 72808-26-5

• 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: (4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicen-4a-carboxamide
• 英文别名: Oleanolic acid amide；3β-hydroxy-olean-12-en-28-oic acid amide；3β-Hydroxy-olean-12-en-28-saeure-amid；3β-Hydroxy-oleanen-(12)-amid-(28)；3β-Hydroxy-oleanen-(12)-saeure-(28)-amid；(4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxamide；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide
• CAS: 72808-26-5
• 化学式: C₃₀H₄₉NO₂
• 分子量: 455.725
• InChiKey: NVQBNTKUZNYNRP-GTOFXWBISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicen-4a-carboxamide 在 lithium aluminium tetrahydride 、 palladium diacetate 、 sodium carbonate 、 三乙胺 、 间氯过氧苯甲酸 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 氟苯 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 tert-butyl (((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-hexadecahydropicen-4a(2H)-yl)methyl)carbamate
  参考文献：
  名称：

  WO2020068689A5

  摘要：

  公开号：

  WO2020068689A5
• 作为产物：
  描述：

  齐墩果酸 在 吡啶 、 草酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 (4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicen-4a-carboxamide
  参考文献：
  名称：

  发现三萜类化合物作为胰脂肪酶和人羧酸酯酶 1 的有效双重抑制剂

  摘要：

  摘要 胰脂肪酶（PL）是众所周知的预防和治疗肥胖的关键靶点。人羧酸酯酶1A（hCES1A）已成为治疗高脂血症的重要靶点。因此，基于 PL 和 hCES1A 的强效双靶点抑制剂的发现对于开发治疗相关代谢疾病的药物具有巨大潜力。在这项研究中，收集了一系列天然三萜类化合物，并使用基于荧光的生化测定法确定了这些三萜类化合物对 PL 和 hCES1A 的抑制作用。发现齐墩果酸（OA）和熊果酸（UA）对PL和hCES1A具有优异的抑制作用，对hCES2A具有较高的选择性。随后，合成并评估了许多基于 OA 和 UA 骨架的化合物。41 ) 对于 PL 和 hCES1A 抑制都非常重要，IC 50分别为 0.75 µM 和 0.014 µM。此外，OA 的 2-烯醇和 3-缩酮部分的化合物39对 PL 和 hCES1A 也有很强的抑制作用，IC 50分别为 2.13 µM 和 0.055 µM。此外，化合

  DOI：

  10.1080/14756366.2022.2029855

文献信息

• Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
  作者：Yi-Nan Zhang、Wei Zhang、Di Hong、Lei Shi、Qiang Shen、Jing-Ya Li、Jia Li、Li-Hong Hu

  DOI：10.1016/j.bmc.2008.07.080

  日期：2008.9

  Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13

  酪氨酸磷酸酶1B蛋白是胰岛素通路负调节的关键因素，也是治疗糖尿病和肥胖症的有希望的靶标。本文中，通过筛选传统中草药文库中鉴定出的针对PTP1B的天然三萜类化合物齐墩果酸，优化了一系列竞争性抑制剂。在3和28位上进行修饰，我们获得了K（i）为130 nM的化合物13，该化合物在除T细胞蛋白酪氨酸磷酸酶以外的其他与胰岛素途径有关的磷酸酶之间表现出良好的选择性。在细胞模型中的进一步评估表明，这些衍生物增强了CHO / hIR细胞中胰岛素受体的磷酸化作用，并刺激了添加或不添加胰岛素的L6肌管中的葡萄糖摄取。
• Synthesis and evaluation of potential complement inhibitory semisynthetic analogs of oleanolic acid
  作者：Haregewein Assefa、Alison Nimrod、Larry Walker、Robert Sindelar

  DOI：10.1016/s0960-894x(99)00314-5

  日期：1999.7

  A number of semisynthetic analogs of oleanolic acid have been synthesized and tested for their complement inhibitory, cytotoxic and apoptotic activities. Among these, compounds 10 and 17 exhibited complement inhibitory potency superior to oleanolic acid. Both have also shown a moderate improvement in in vitro therapeutic index (T.I.). (C) 1999 Elsevier Science Ltd. All rights reserved.
• Kuwada, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1931, vol. 51, p. 462,494<, dtsch. Ref. S. 57, 59, 69
  作者：Kuwada

  DOI：——

  日期：——
• Free hemoglobin concentrations in patients receiving massive blood transfusion during emergency surgery for trauma
  作者：Tomoki Nishiyama、Kazuo Hanaoka

  DOI：10.1007/bf03019668

  日期：2000.9

  Purpose: To determine free hemoglobin concentration in patients who received massive blood transfusion during emergency surgery for trauma with consideration of the storage of the transfused blood.Methods: Fifteen patients undergoing emergency surgery for multiple trauma and who received blood transfusion of more than 5,000 mt were studied. Transfusion of the stored whole blood in citrate-phosphate glucose solution using a micropore filter was started before surgery. Serum concentrations of hemoglobin (total:THb and free:fHb) and total haptoglobin (THp) were measured until 5,000 mt of blood had been transfused. Serum free haptoglobin (fHp) concentration was calculated. The correlation between the changes in hemoglobin or haptoglobin concentrations and total storage days of the transfused blood was analyzed by a simple regression analysis.Results: Free hemoglobin was detected after 2,000 mt transfusion. The THp and fHp decreased after 1,000 mt transfusion. Total storage time (days) of transfused blood had correlated with the changes of THp (P < 0.0001) and fHp (P = 0.0027) but not with the changes of THb (P = 0.984) and fHb (P = 0.834).Conclusion: After blood transfusion during surgery for trauma, serum haptoglobin concentration decreased with transfusion of greater than or equal to 1,000 mt of whole blood with mean storage time of 12.2 dy. Free hemoglobin was detected after 2,000 mt transfusion when THp decreased to 1,000 mg L-l. Serum haptoglobin concentrations correlated negatively with storage time (days) of transfused blood.
• 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.