indole[3,2-b]olean-12-en-28-oic acid | 577994-82-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: indole[3,2-b]olean-12-en-28-oic acid
• 英文别名: [3,2-b]indoleolean-12-en-28-oic acid；indole[3,2-b]olean-12-ene-28-formic acid；[3,2-b]indole oleanolic acid；(1R,2R,14R,17R,18S,21S,26S)-2,13,13,17,18,24,24-heptamethyl-11-azaheptacyclo[15.12.0.02,14.04,12.05,10.018,27.021,26]nonacosa-4(12),5,7,9,27-pentaene-21-carboxylic acid
• CAS: 577994-82-2
• 化学式: C₃₆H₄₉NO₂
• 分子量: 527.791
• InChiKey: CYZDIVSPGGJBHB-FDWPCWODSA-N

物化性质

• 熔点：
  229-230 °C
• 沸点：
  644.3±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  39
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  indole[3,2-b]olean-12-en-28-oic acid 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(1R,2R,14R,17R,18S,21S,26S)-2,13,13,17,18,24,24-heptamethyl-11-azaheptacyclo[15.12.0.02,14.04,12.05,10.018,27.021,26]nonacosa-4(12),5,7,9,27-pentaen-21-yl]-morpholin-4-ylmethanone
  参考文献：
  名称：

  齐墩果酸和熊果酰胺的新型 A 环查耳酮衍生物，具有通过 ROS 触发的细胞凋亡介导的抗增殖作用

  摘要：

  一系列A环改性齐墩果酸和熊果酸衍生物，包括C28酰胺（3-氧代-C2-烟酰基/糠基、3β-羟基-C2-烟酰基、3β-烟酰氧基-、2-氰基-3,4-seco-4合成（23）-烯、吲哚-、内酰胺和氮杂环庚烷）并筛选其针对 NCI-60 癌细胞系组的细胞毒活性。对 32 种测试化合物的第一次测定结果表明，11 种衍生物对癌细胞表现出细胞毒性，其中 6 种被选择进行完整的剂量反应研究。通过使用网络相似图对合成化合物之间的效力分布和相似关系进行比较分析，对局部 SAR 进行了系统研究。在齐墩果烷型三萜类化合物中，C2-[4-亚吡啶]-齐墩果酸 C28-吗啉酰胺对 15 种不同的肿瘤细胞系表现出亚微摩尔效力，并对非小细胞肺癌 (HOP-92) 具有特殊选择性，GI 为50值为 0.0347 μM。另一方面，C2-[3-pyridinylidene]-ursonic N -methyl-piperazinyl

  DOI：

  10.3390/ijms22189796
• 作为产物：
  描述：

  齐墩果酸 在 Jones reagent 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 indole[3,2-b]olean-12-en-28-oic acid
  参考文献：
  名称：

  齐墩果酸衍生物-查尔酮共轭物作为α-葡萄糖苷酶抑制剂的合成和生物学评估†

  摘要：

  α-葡萄糖苷酶是治疗肥胖症和糖尿病的有希望的靶标。设计并合成了一系列齐墩果酸衍生物-查耳酮共轭物，作为α-葡萄糖苷酶抑制剂。通过光谱分析确定其结构，并在体外研究其对α-葡萄糖苷酶的抑制活性。大多数缀合物对α-葡萄糖苷酶表现出中等的抑制活性。其中，缀合物1b（IC 50= 3.2±0.2μM）具有最强的α-葡萄糖苷酶抑制活性，初步的构效关系表明，缀合物查尔酮单元中的呋喃环或噻吩环具有增强活性的趋势。Lineweaver-Burk图分析表明1b，6b，5c和4d竞争性抑制了α-葡萄糖苷酶的活性。它们的抑制常数（K i）分别为16.6、29.3、14.6和20.6μM。结合物和α-葡萄糖苷酶之间的相互作用力是氢键和范德华力。

  DOI：

  10.1039/c3ra46492j

文献信息

• Synthesis and evaluation of 2,3-indolotriterpenoids as new α-glucosidase inhibitors
  作者：Elmira F. Khusnutdinova、Irina E. Smirnova、Oxana B. Kazakova、Anastasiya V. Petrova、Nguyen Thi Thu Ha、Do Quoc Viet

  DOI：10.1007/s00044-017-1972-0

  日期：2017.11

  AbstractA series of ring-A fused heterocycles of lupane, oleanane, ursane and dammarane triterpenoids were synthesized and evaluated for their inhibitory activity against α-glucosidase. An influence of the different types of triterpenoids with indole and pyrazine cycles on the activity was revealed. Among them, 2,3-indolo-lup-20(29)-en-28-oic acid with an IC50 of 1.8 µM was the most active compound

  摘要合成了一系列环戊烷，齐墩果烷，乌尔烷和达玛烷三萜类化合物的A环稠合杂环，并评估了其对α-葡萄糖苷酶的抑制活性。揭示了吲哚和吡嗪循环不同类型的三萜类化合物对活性的影响。其中，IC 50为1.8 µM的2,3-吲哚-lup-20（29）-en-28-油酸是活性最高的化合物，其活性是市售阿卡波糖的221倍。在大多数情况下，用吡嗪片段取代吲哚会降低活性（除了达玛烷型吡嗪衍生物）。 图形概要
• Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity
  作者：Jun-Feng Li、Yu Zhao、Min-Min Cai、Xiao-Fei Li、Jian-Xin Li

  DOI：10.1016/j.ejmech.2008.12.024

  日期：2009.7

  Oleanolic acid with anti-bone resorption effect was an active component discovered in a medicinal plant of Achyranthes bidentata. A series of heterocyclic derivatives of oleanolic acid including indole, pyrazine, quinoxaline, quinoline moieties and their natural amino acid amides were synthesized. Their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) and cytotoxicity

  具有抗骨吸收作用的齐墩果酸是在牛膝的药用植物中发现的活性成分。合成了一系列齐墩果酸的杂环衍生物，包括吲哚，吡嗪，喹喔啉，喹啉部分及其天然氨基酸酰胺。评估了它们对破骨细胞样多核细胞（OCL）形成的抑制活性以及所选衍生物的细胞毒性。在衍生物中，化合物2a和8a即使在200 nM时也显示出相当强的活性。还讨论了衍生物的结构-活性关系。
• Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B
  作者：Wen-Wei Qiu、Qiang Shen、Fan Yang、Bo Wang、Hui Zou、Jing-Ya Li、Jia Li、Jie Tang

  DOI：10.1016/j.bmcl.2009.10.017

  日期：2009.12

  A series of maslinic acid derivatives have been synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Most of the compounds exhibited a dramatic increase in inhibitory potency and selectivity, the two most potent PTP1B inhibitors 20 (IC50 = 0.61 mu M) and 29 (IC50 = 0.64 mu M) showed about 10-fold more potent than lead compound maslinic acid. More importantly, 29 possesses the best selectivity of 6.9-fold for PTP1B over TCPTP. (C) 2009 Elsevier Ltd. All rights reserved.
• Oleanolic acid analogs as NO, TNF-α and IL-1β inhibitors: Synthesis, biological evaluation and docking studies
  作者：Pamita Bhandari、Neeraj Kumar Patel、Rahul P. Gangwal、Abhay T. Sangamwar、Kamlesh Kumar Bhutani

  DOI：10.1016/j.bmcl.2014.07.056

  日期：2014.9

  A series of oleanolic acid analogs, characterized by structural modifications at position C-3 and C-28 of oleanane skeleton were synthesized and assessed for antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophages. Results revealed that all the synthesized analogs of oleanolic acid inhibit NO production with an IC50 of 2.66-41.7 μM as compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50=69.21 and 73.18 μM on RAW 264.7 and J774A.1 cells, respectively) without affecting the cell viability when tested at their half maximal concentration. The most potent NO inhibitors (2, 8, 9 and 10) at a concentration of 20 μg/mL also demonstrated mild inhibition (27.9-51.9%) of LPS-induced tumor necrosis factor alpha (TNF-α) and weak inhibition (11.1-37.5%) towards interleukin 1-beta (IL-1β) production in both the cells. The present study paves a direction that analogs of oleanolic acid can be employed as a lead in the development of potent NO inhibitors. Molecular docking studies also showed that 10 (with top Goldscore docking pose 19.05) showed similar interaction as that of co-crystallized inhibitor and, thereby, helps to design the potent inhibitors of TNF-α.
• Glycoside modification of oleanolic acid derivatives as a novel class of anti-osteoclast formation agents
  作者：Jun-Feng Li、Song-Jie Chen、Yu Zhao、Jian-Xin Li

  DOI：10.1016/j.carres.2009.01.019

  日期：2009.3

  Oleanolic acid, a natural product, possesses an anti-osteoclast formation activity. Targeting at discovery of novel and potent anti-bone resorption agents, 22 glycosides of oleanolic acid derivatives (including D-galactopyranosides, D-glucopyranosides, D-xylopyranoses, D-arabopyranoses and D-glycuronic acids) were synthesized at phase-transfer-catalyzed conditions (K2CO3, Bu4NBr, CH2Cl2-H2O) and their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) induced by 1 alpha,25-dihydroxyvitamin D-3 was evaluated in a co-culture assay system. The structure-activity relationships of these compounds were also discussed. (C) 2009 Elsevier Ltd. All rights reserved.