methyl (13S,15S,17S)-13-[(1'R,5S,9'R,11'R,12'R,19'R)-11'-acetyloxy-3-(2-chloroethyl)-12'-ethyl-5'-methoxy-8'-methyl-2,4-dioxospiro[1,3-oxazolidine-5,10'-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene]-4'-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate | 67699-40-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 长春花生物碱
• 英文名称: methyl (13S,15S,17S)-13-[(1'R,5S,9'R,11'R,12'R,19'R)-11'-acetyloxy-3-(2-chloroethyl)-12'-ethyl-5'-methoxy-8'-methyl-2,4-dioxospiro[1,3-oxazolidine-5,10'-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene]-4'-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate
• CAS: 67699-40-5
• 化学式: C₄₈H₅₈ClN₅O₉
• 分子量: 884.5
• InChiKey: MMRCWWRFYLZGAE-JBJHZRFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  63
• 可旋转键数：
  10
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  12

文献信息

• Cobalamin conjugates for anti-tumor therapy
  申请人：Weinshenker M. Ned

  公开号：US20050054607A1

  公开（公告）日：2005-03-10

  The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.

  本发明提供了一种适用于治疗肿瘤相关疾病的钴胺素-药物结合物。钴胺素通过可切割的连接剂间接共价结合到抗肿瘤药物上，还可以通过一个或多个可选的间隔物。钴胺素通过其核糖环的5'-OH与第一间隔物或可切割连接剂共价结合。药物通过其现有或添加的功能基团与可切割连接剂的第二间隔物结合。在给药后，结合物与转钴胺素（其任何同工异构体）形成复合物。然后，该复合物结合到细胞膜上的受体并被细胞摄取。一旦进入细胞，细胞内酶将切割结合物，从而释放药物。根据结合物的结构，特定类别或类型的细胞内酶影响切割。由于生长细胞对钴胺素的需求量较高，肿瘤细胞通常摄取结合物的比例高于正常非生长细胞。本发明的结合物与相应的游离药物相比，具有较低的全身毒性和增强的疗效。
• [EN] DIHYDROPYRROLONAPHTYRIDINONE COMPOUNDS AS INHIBITORS OF JAK<br/>[FR] COMPOSÉS DE DIHYDROPYRROLONAPHTYRIDINONE COMME INHIBITEURS DE JAK
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010144486A1

  公开（公告）日：2010-12-16

  Disclosed are JAK inhibitors of formula (I) where G1, R1, R2, R3, R4, R5, R6, and R7 are defined in the specification. Also disclosed are pharmaceutical compositions, kits and articles of manufacture which contain the compounds, methods and materials for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other diseases, disorders or conditions associated with JAK.

  揭示了式(I)的JAK抑制剂，其中G1、R1、R2、R3、R4、R5、R6和R7在规范中定义。还披露了含有这些化合物的药物组合物、试剂盒和制造物品，制备这些化合物的方法和材料，以及使用这些化合物治疗涉及免疫系统和炎症的疾病、紊乱和症状的方法，包括类风湿关节炎、血液恶性肿瘤、上皮癌（即癌症）和其他与JAK相关的疾病、紊乱或症状。
• [EN] SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS DE PYRIDAZINECARBOXAMIDE SUBSTITUÉS UTILES EN TANT QUE COMPOSÉS INHIBITEURS DE KINASE
  申请人：XCOVERY INC

  公开号：WO2009154769A1

  公开（公告）日：2009-12-23

  Pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.

  吡啶并呋嗪衍生物作为蛋白激酶抑制剂具有意想不到的药物特性，并可用于治疗与异常蛋白激酶活性相关的疾病，如癌症。
• [EN] AZOLE COMPOUNDS AS PIM INHIBITORS<br/>[FR] COMPOSÉS D'AZOLE UTILISÉS EN TANT QU'INHIBITEURS DES PIM
  申请人：AMGEN INC

  公开号：WO2012129338A1

  公开（公告）日：2012-09-27

  The invention relates to bicyclic compounds of formulas I and Ia, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

  该发明涉及公式I和Ia的双环化合物及其盐。在某些实施例中，该发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文所披露的化合物的药物组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症中的用途。
• [EN] AZAINDOLE DERIVATIVES WHICH ACT AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS D'AZAINDOLE AGISSANT COMME INHIBITEUR DE PI3K
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2014011568A1

  公开（公告）日：2014-01-16

  Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating immunological disorders, cardiovascular disease, cancer, and other diseases, disorders or conditions associated with PI3Kδ.

  揭示了Formula 1的化合物及其药用盐，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10在规范中有定义。本公开还涉及制备Formula 1化合物的材料和方法，含有它们的药物组合物，以及它们用于治疗免疫性疾病、心血管疾病、癌症和与PI3Kδ相关的其他疾病、疾患或症状的用途。