lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oic acid | 936617-74-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oic acid
• 英文别名: (1R,2R,11R,14R,15R,18S,21R,22R,23R)-2,10,10,14,15-pentamethyl-21-prop-1-en-2-yl-5,8-diazahexacyclo[12.11.0.02,11.04,9.015,23.018,22]pentacosa-4,6,8-triene-18-carboxylic acid
• CAS: 936617-74-2
• 化学式: C₃₂H₄₆N₂O₂
• 分子量: 490.729
• InChiKey: XRICJCSDSSJSBM-JOQCCHAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oyl chloride
  参考文献：
  名称：

  杂环融合的卢烷三萜类化合物可抑制利什曼原虫donovani amastigotes †

  摘要：

  报道了杂环桦木素衍生物的合成及其对利什曼原虫的活性。丁二酸用作通用中间体。在异戊烷骨架的2,3-位引入了几个不同的稠合杂环，包括异恶唑，吡嗪，吡啶，吲哚和吡唑环。同样，对28位进行了修改。三种化合物，5，8和25，显示出低的微摩尔活性，IC 50个分别为13.2，4.3和7.2μM，值。化合物8表现出最佳的活性和选择性，并使用5μM的浓度在受感染的巨噬细胞上测试了其活性，没有显示出巨噬细胞毒性。有趣的是，化合物8对轴突性变形虫和利什曼原虫感染的巨噬细胞的活性是相似的。

  DOI：

  10.1039/c3md00282a
• 作为产物：
  描述：

  白桦脂酸 在 吗啉 、 chromium(VI) oxide 、 sulfur 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oic acid
  参考文献：
  名称：

  Triterpenoid Pyrazines and Benzopyrazines with Cytotoxic Activity

  摘要：

  Twelve lupane, 18 alpha-oleanane, and des-E-lupane derivatives (1a-5b) were either extracted from natural sources or synthesized from betulinic acid (1a) and betulin (2). Compounds 1b, 1c, 3b, 3c, 4b, 4c, 5a, and 5b were then used as starting materials for further synthesis of a series of pyrazines and benzopyrazines (6a-18); 20 of them are new (6a-6e, 7a-7d, and 10a-18). Activity of pyrazine 6a against the T-lymphoblastic leukemia cell line CEM encouraged us to synthesize several new esters (6b-6d) to study structure-activity relationships with respect to substitution of the carboxyl group at position 28. The synthesized compounds were tested for cytotoxicity against a variety of cancer cell lines of different histogenetic origin, and the results were compared with cytotoxicity of the known starting compounds. Significant cytotoxic activity against A 549, K 562, and multidrug-resistant K 562-tax cell lines was found in pyrazines 6a, 6d, and 6e.

  DOI：

  10.1021/np060436d

文献信息

• Synthesis and Biological Evaluation of Heterocyclic Ring-Fused Betulinic Acid Derivatives as Novel Inhibitors of Osteoclast Differentiation and Bone Resorption
  作者：Jun Xu、Zhenxi Li、Jian Luo、Fan Yang、Ting Liu、Mingyao Liu、Wen-Wei Qiu、Jie Tang

  DOI：10.1021/jm201540h

  日期：2012.4.12

  A series of betulinic acid (BA) derivatives were designed and synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects of RANKL-induced osteoclastogenesis were evaluated by using a cell-based tartrate-resistant acid phosphatase (TRAP) activity assay. To our delight, most of these compounds exhibited a dramatic increase in inhibitory potency, compared

  通过在C-2和C-3位置引入各种稠合杂环，设计和合成了一系列桦木酸（BA）衍生物。通过使用基于细胞的抗酒石酸酸性磷酸酶（TRAP）活性测定，评估了它们对RANKL诱导的破骨细胞形成的抑制作用。令我们高兴的是，与BA相比，这些化合物中的大多数都显示出显着的抑制效能。最有效的化合物20即使在0.1μM的低浓度下也显示出66.9％的抑制作用，其效力比前导化合物BA高约200倍。此外，RAW264.7的细胞毒性试验表明20对破骨细胞分化的抑制作用不是由其细胞毒性引起的。初步的力学研究表明，20可以抑制组织蛋白酶K和TRAP的破骨细胞生成相关标志物基因表达水平。更重要的是，20可以减轻卵巢切除小鼠体内的骨质流失。因此，这些BA衍生物可用作开发新型抗骨质疏松剂的潜在先导。
• A Synthetic Approach for the Rapid Preparation of BODIPY Conjugates and their use in Imaging of Cellular Drug Uptake and Distribution
  作者：Sona Krajcovicova、Jarmila Stankova、Petr Dzubak、Marian Hajduch、Miroslav Soural、Milan Urban

  DOI：10.1002/chem.201706093

  日期：2018.4.3

  A solid‐phase synthetic (SPS) method was developed for the preparation of BODIPY‐labeled bioactive compounds that allows for fast and simple synthesis of conjugates for use in fluorescent microscopy. The approach was used to visualize cellular uptake and distribution of cytotoxic triterpenes in cancer cells.

  开发了一种固相合成（SPS）方法来制备BODIPY标记的生物活性化合物，该方法可快速简便地合成用于荧光显微镜的结合物。该方法用于可视化癌细胞中细胞摄取和细胞毒性三萜的分布。
• Triterpenoid pyrazines and pyridines – Synthesis, cytotoxicity, mechanism of action, preparation of prodrugs
  作者：Jiří Hodoň、Ivo Frydrych、Zdeňka Trhlíková、Jan Pokorný、Lucie Borková、Sandra Benická、Martin Vlk、Barbora Lišková、Agáta Kubíčková、Martina Medvedíková、Martin Pisár、Jan Šarek、Viswanath Das、Anna Ligasová、Karel Koberna、Petr Džubák、Marián Hajdúch、Milan Urban

  DOI：10.1016/j.ejmech.2022.114777

  日期：2022.12

  A set of fifteen triterpenoid pyrazines and pyridines was prepared from parent triterpenoid 3-oxoderivatives (betulonic acid, dihydrobetulonic acid, oleanonic acid, moronic acid, ursonic acid, heterobetulonic acid, and allobetulone). Cytotoxicity of all compounds was tested in eight cancer and two non-cancer cell lines. Evaluation of the structure-activity relationships revealed that the triterpenoid

  由母体三萜类 3-氧代衍生物（桦木酸、二氢桦木酸、齐墩果酸、木糖酸、熊果酸、杂桦木酸和别木酮）制备了一组十五种三萜类吡嗪和吡啶。在八种癌症和两种非癌细胞系中测试了所有化合物的细胞毒性。对构效关系的评估表明，三萜核心决定了最终分子是否具有活性，而杂环能够增加活性并调节特异性。五种化合物（1b、1c、2b、2c和8）被发现具有优先和高度细胞毒性（IC 50 ≈ 1 μM) 抗白血病癌细胞系（CCRF-CEM、K562、CEM-DNR 或 K562-TAX）。令人惊讶的是，化合物1c、2b和2c在耐多药白血病细胞（CEM-DNR 和 K562-TAX）中的活性比在其非耐药类似物（CCRF-CEM 和 K562）中的活性高 10 倍。测量了最有希望的候选药物的药理参数，并合成了两种类型的前药：1）含糖缀合物，其中大部分具有改善细胞穿透性并在 CCRF-CEM 细胞系中保持高细胞毒性，不幸的是，它们失去了对抗性细胞。2)
• Triterpenoid Pyrazines and Benzopyrazines with Cytotoxic Activity
  作者：Milan Urban、Jan Sarek、Miroslav Kvasnica、Iva Tislerova、Marian Hajduch

  DOI：10.1021/np060436d

  日期：2007.4.1

  Twelve lupane, 18 alpha-oleanane, and des-E-lupane derivatives (1a-5b) were either extracted from natural sources or synthesized from betulinic acid (1a) and betulin (2). Compounds 1b, 1c, 3b, 3c, 4b, 4c, 5a, and 5b were then used as starting materials for further synthesis of a series of pyrazines and benzopyrazines (6a-18); 20 of them are new (6a-6e, 7a-7d, and 10a-18). Activity of pyrazine 6a against the T-lymphoblastic leukemia cell line CEM encouraged us to synthesize several new esters (6b-6d) to study structure-activity relationships with respect to substitution of the carboxyl group at position 28. The synthesized compounds were tested for cytotoxicity against a variety of cancer cell lines of different histogenetic origin, and the results were compared with cytotoxicity of the known starting compounds. Significant cytotoxic activity against A 549, K 562, and multidrug-resistant K 562-tax cell lines was found in pyrazines 6a, 6d, and 6e.
• Heterocycle-fused lupane triterpenoids inhibit <i>Leishmania donovani</i> amastigotes
  作者：Raisa Haavikko、Abedelmajeed Nasereddin、Nina Sacerdoti-Sierra、Dmitry Kopelyanskiy、Sami Alakurtti、Mari Tikka、Charles L. Jaffe、Jari Yli-Kauhaluoma

  DOI：10.1039/c3md00282a

  日期：——

  The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar

  报道了杂环桦木素衍生物的合成及其对利什曼原虫的活性。丁二酸用作通用中间体。在异戊烷骨架的2,3-位引入了几个不同的稠合杂环，包括异恶唑，吡嗪，吡啶，吲哚和吡唑环。同样，对28位进行了修改。三种化合物，5，8和25，显示出低的微摩尔活性，IC 50个分别为13.2，4.3和7.2μM，值。化合物8表现出最佳的活性和选择性，并使用5μM的浓度在受感染的巨噬细胞上测试了其活性，没有显示出巨噬细胞毒性。有趣的是，化合物8对轴突性变形虫和利什曼原虫感染的巨噬细胞的活性是相似的。