葛杜宁 | 2753-30-2

• 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
• 中文名称: 葛杜宁
• 中文别名: 格杜宁
• 英文名称: gedunin
• 英文别名: [(1S,2R,4S,7S,8S,11R,12R,17R,19R)-7-(furan-3-yl)-1,8,12,16,16-pentamethyl-5,15-dioxo-3,6-dioxapentacyclo[9.8.0.02,4.02,8.012,17]nonadec-13-en-19-yl] acetate
• CAS: 2753-30-2
• 化学式: C₂₈H₃₄O₇
• 分子量: 482.574
• InChiKey: YJXDGWUNRYLINJ-BHAPSIHVSA-N

物化性质

• 熔点：
  218 °C(Solv: methanol (67-56-1))
• 沸点：
  594.3±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）
• LogP：
  3.201 (est)
• 碰撞截面：
  205.7 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  95.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  葛杜宁 在 sodium tetrahydroborate 、 cerium trichloride hexahydrate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 0.05h， 以93%的产率得到(1S,3aS,41R,4a1S,5R,10aS,12aS)-1-(furan-3-yl)-3,8-dihydroxy-4a1,7,7,10a,12a-pentamethyl-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl acetate
  参考文献：
  名称：

  Gedunin, a Novel Hsp90 Inhibitor: Semisynthesis of Derivatives and Preliminary Structure−Activity Relationships

  摘要：

  Gedunin (1), a tetranortriterpenoid isolated from the Indian neern tree (Azadirachta indica), was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors. The mechanism of action by which gedunin induces client protein degradation remains undetermined, however, prior studies have demonstrated that it does not bind competitively versus ATP. In an effort to further probe the mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells determined. Although no compound was found to exhibit antiproliferative activity more effective than the natural product, functionalities critical for antiproliferative activity have been identified.

  DOI：

  10.1021/jm8007486
• 作为产物：
  描述：

  C₂₆H₃₆O₅ 在 氧气 、 palladium diacetate 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 、 乙基苯 为溶剂， 反应 18.08h， 生成 葛杜宁
  参考文献：
  名称：

  Concise Chemoenzymatic Synthesis of Gedunin

  摘要：

  DOI：

  10.1021/jacs.2c09048

文献信息

• [EN] SUBSTITUTED INDAZOLE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH<br/>[FR] COMPOSÉS INDAZOLE SUBSTITUÉS , COMPOSITIONS LES CONTENANT ET MÉTHODES DE TRAITEMENT AU MOYEN DESDITS COMPOSÉS
  申请人：CELGENE CORP

  公开号：WO2016089977A1

  公开（公告）日：2016-06-09

  Provided herein are methods for treating and preventing malaria and/or Babesiosis, the methods comprising administering an effective amount of Indazole Compounds having the formulas: (I)[Formula (I) should be inserted here] or (II)[Formula (II) should be inserted here] wherein R1, R2, R3 and Y are as defined herein.

  提供的方法用于治疗和预防疟疾和/或巴贝虫病，这些方法包括施用有效量的吲唑化合物，其具有以下公式：(I) [在此处插入公式(I)]或(II) [在此处插入公式(II)]，其中R1、R2、R3和Y如本文所述定义。
• [EN] MALT1 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE MALT1 ET LEURS UTILISATIONS
  申请人：UNIV CORNELL

  公开号：WO2017040304A1

  公开（公告）日：2017-03-09

  Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin' s lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis,an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

  本文提供了化合物的化学式(I)及其药物组合物，可用作MALT1抑制剂。还提供了通过给予化合物的化学式(I)来治疗增生性疾病（例如癌症（例如非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤、MALT淋巴瘤）、良性肿瘤、与血管生成有关的疾病、自身免疫疾病、炎症性疾病、自身炎症性疾病）的方法。
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015069693A1

  公开（公告）日：2015-05-14

  The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及抑制组蛋白去乙酰化酶活性的化合物以及合成这些化合物的方法。本发明还涉及含有这些化合物的药物组合物。本发明还涉及通过向需要的受试者施用这些化合物和药物组合物来治疗和预防血液细胞增生性疾病，如多发性骨髓瘤的方法。
• TARGETED THERAPEUTICS
  申请人：Chimmanamada Dinesh U.

  公开号：US20140079636A1

  公开（公告）日：2014-03-20

  The present invention provides pharmacological compounds including an effector moiety conjugated to an binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供了药理化合物，包括将效应器基团偶联到结合基团上，以将效应器基团定向到感兴趣的生物靶点。同样，本发明提供了包括该化合物的组合物、试剂盒和方法（例如治疗、诊断和成像）。该化合物可以被描述为蛋白质相互作用的结合基团-药物偶联物（SDC-TRAP）化合物，包括蛋白质相互作用的结合基团和效应器基团。例如，在治疗癌症的某些实施方案中，SDC-TRAP可以包括Hsp90抑制剂与细胞毒素剂作为效应器基团的偶联物。
• INHIBITORS OF HISTONE DEACETYLASE
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160272579A1

  公开（公告）日：2016-09-22

  The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及抑制组蛋白去乙酰化酶活性的化合物及其合成方法。本发明还涉及含有这些化合物的制药组合物。本发明还涉及通过向需要治疗和预防血液细胞增殖性疾病（如多发性骨髓瘤）的受试者给予这些化合物和制药组合物的方法。