7-benzyl-4-chloro-2-methyl-5H-pyrrolo[3,2-d]pyrimidine | 1392817-33-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 7-benzyl-4-chloro-2-methyl-5H-pyrrolo[3,2-d]pyrimidine
• 英文别名: 7-Benzyl-4-chloro-2-methyl-5H-pyrrolo[3,2-d]pyrimidine
• CAS: 1392817-33-2
• 化学式: C₁₄H₁₂ClN₃
• 分子量: 257.722
• InChiKey: FVHXQTFWEXHYGT-UHFFFAOYSA-N

物化性质

• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-benzyl-4-chloro-2-methyl-5H-pyrrolo[3,2-d]pyrimidine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 15.25h， 生成 7-benzyl-N-(4-methoxyphenyl)-2,5-dimethyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine hydrochloride
  参考文献：
  名称：

  7-苄基-N-（取代）-吡咯并[3,2-d]嘧啶-4-胺作为单一药物的发现和临床前评估，具有微管靶向作用以及作为抗肿瘤药物的三效血管激酶抑制作用

  摘要：

  细胞抑制剂抗血管生成剂（AA）在癌症化疗中的用途在于它们与细胞毒性化疗剂的组合。AA 与微管靶向剂 (MTA) 的临床组合尤其成功。报道了一系列 7-苄基-N-取代-吡咯并[3,2- d ]嘧啶-4-胺的发现、合成和生物学评价。抑制促血管生成受体酪氨酸激酶 (RTK) 的新型化合物，包括血管内皮生长因子受体-2 (VEGFR-2)、血小板源性生长因子受体-β (PDGFR-β) 和表皮生长因子受体 (EGFR) 以及微管描述了单分子靶向。这些化合物还在鸡绒毛尿囊膜 (CAM) 测定中抑制血管形成，并且一些化合物有效抑制微管蛋白组装（其活性与考布他汀 A-4 (CA) 相当）。此外，一些类似物还规避了临床上最相关的肿瘤对微管靶向剂 (MTA) 的耐药机制（P-糖蛋白和 β-III 微管蛋白表达）。这些 MTA 结合在微管蛋白上的秋水仙碱位点。两种类似物在整个 NCI 60 肿瘤细胞组中显示出两到三位数的纳摩尔

  DOI：

  10.1016/j.bmc.2016.11.026
• 作为产物：
  描述：

  methyl 3-amino-4-benzyl-1H-pyrrole-2-carboxylate 在 盐酸 、 三氯氧磷 作用下， 反应 6.25h， 生成 7-benzyl-4-chloro-2-methyl-5H-pyrrolo[3,2-d]pyrimidine
  参考文献：
  名称：

  Substituted Bicyclic Pyrimidine Compounds with Tubulin and Multiple Receptor Inhibition

  摘要：

  这项发明提供了替代的双环嘧啶化合物及其药用盐、水合物和溶剂合物，每种化合物具有微管和多重受体抑制特性。公开了治疗诊断为癌症的患者的方法，包括向患者投予治疗有效量的替代的双环嘧啶化合物和其药用盐、水合物和溶剂合物，用于治疗癌症。

  公开号：

  US20150284398A1

文献信息

• Substituted bicyclic pyrimidine compounds with tubulin and multiple receptor inhibition
  申请人：Duquesne University of the Holy Spirit

  公开号：US10358450B2

  公开（公告）日：2019-07-23

  This invention provides substituted bicyclic pyrimidine compounds and pharmaceutically acceptable salts, hydrates, and solvates of the compounds, each having tubulin and multiple receptor inhibition properties. Methods of treating a patient diagnosed with cancer is disclosed comprising administering to the patient a therapeutically effective amount of the substituted bicyclic pyrimidine compounds and pharmaceutically acceptable salts, hydrates, and solvates of the compounds, for treating cancer.

  本发明提供了取代的双环嘧啶化合物和这些化合物的药学上可接受的盐、水合物和溶液，每种化合物都具有抑制小管蛋白和多种受体的特性。本发明公开了治疗被诊断患有癌症的患者的方法，包括向患者施用治疗有效量的取代双环嘧啶化合物和该化合物的药学上可接受的盐、水合物和溶液来治疗癌症。
• Discovery of Antitubulin Agents with Antiangiogenic Activity as Single Entities with Multitarget Chemotherapy Potential
  作者：Aleem Gangjee、Roheeth Kumar Pavana、Michael A. Ihnat、Jessica E. Thorpe、Bryan C. Disch、Anja Bastian、Lora C. Bailey-Downs、Ernest Hamel、Rouli Bai

  DOI：10.1021/ml4004793

  日期：2014.5.8

  Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI(50) values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.
• SUBSTITUTED BICYCLIC PYRIMIDINE COMPOUNDS WITH TUBULIN AND MULTIPLE RECEPTOR INHIBITION
  申请人：Duquesne University of the Holy Spirit

  公开号：EP3125899A1

  公开（公告）日：2017-02-08
• BICYCLIC AND TRICYCLIC PYRIMIDINE TYROSINE KINASE INHIBITORS WITH ANTITUBULIN ACTIVITY AND METHODS OF TREATING A PATIENT
  申请人：Gangjee Aleem

  公开号：US20120264768A1

  公开（公告）日：2012-10-18

  Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity are provided in the present invention. The compositions of the present invention possess dual activity in a single agent of potent vascular endothelial growth factor receptor inhibitory activity as well as antitubulin activity. Water soluble salts of these compositions are also described. Methods of treating a patient having cancer, macular degeneration, and arthritis with the compositions and salts thereof of the present invention are disclosed.
• [EN] SUBSTITUTED BICYCLIC PYRIMIDINE COMPOUNDS WITH TUBULIN AND MULTIPLE RECEPTOR INHIBITION<br/>[FR] COMPOSÉS DE PYRIMIDINE BICYCLIQUES SUBSTITUÉS PAR DE LA TUBULINE ET INHIBITION DE MULTIPLES RÉCEPTEURS
  申请人：UNIV HOLY GHOST DUQUESNE

  公开号：WO2015153955A1

  公开（公告）日：2015-10-08

  This invention provides substituted bicyclic pyrimidine compounds and pharmaceutically acceptable salts, hydrates, and solvates of the compounds, each having tubulin and multiple receptor inhibition properties. Methods of treating a patient diagnosed with cancer is disclosed comprising administering to the patient a therapeutically effective amount of the substituted bicyclic pyrimidine compounds and pharmaceutically acceptable salts, hydrates, and solvates of the compounds, for treating cancer.