2,4-dichloro-7-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidine | 1255939-53-7

• 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: 2,4-dichloro-7-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 2,4-Dichloro-7-[(4-methoxyphenyl)methyl]pyrrolo[2,3-d]pyrimidine
• CAS: 1255939-53-7
• 化学式: C₁₄H₁₁Cl₂N₃O
• 分子量: 308.167
• InChiKey: ZYVWOGISUDPGKR-UHFFFAOYSA-N

物化性质

• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-7-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2,2,2-三氟乙醇 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 乙二醇甲醚 、 甲苯 为溶剂， 反应 101.0h， 生成 N-isopropyl-2-((2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)-7-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  一种间变性淋巴瘤激酶抑制剂及其制备方法 和用途

  摘要：

  本发明涉及式(I)化合物及其药物组合物和制备方法，其可用作ALK抑制剂来治疗由ALK介导的疾病。本发明还涉及式(I)化合物的制备方法，以及式(I)化合物及其药物组合物在制备治疗由ALK介导的疾病的药物中的应用。

  公开号：

  CN107936024B
• 作为产物：
  描述：

  2,4-二氯-7H吡咯[2,3-D]嘧啶 、 4-甲氧基氯苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以21%的产率得到2,4-dichloro-7-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  [EN] HETEROCYCLIC HYDROXAMIC ACIDS AS PROTEIN DEACETYLASE INHIBITORS AND DUAL PROTEIN DEACETYLASE-PROTEIN KINASE INHIBITORS AND METHODS OF USE THEREOF
  [FR] ACIDES HYDROXAMIQUES HÉTÉROCYCLIQUES COMME INHIBITEURS DE PROTÉINE DÉSACÉTYLASE ET INHIBITEURS DOUBLES DE PROTÉINE KINASE-PROTÉINE DÉSACÉTYLASE, ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本发明涉及一种新型的羟羧胺酸，它们是特异的组蛋白去乙酰化酶（HDAC）抑制剂和/或TTK/Mps1激酶抑制剂，包括其药用盐，用于调节HDAC和/或TTK/Mps1激酶活性，包括这些化合物的制药组合物，以及其制备方法。

  公开号：

  WO2015175813A1

文献信息

• Heterobicyclic inhibitors of transforming growth factor beta receptor I (TGFβRI)
  作者：Lalgudi S. Harikrishnan、Jayakumar Warrier、Andrew J. Tebben、Gopikishan Tonukunuru、Sudhakara R. Madduri、Vishweshwaraiah Baligar、Raju Mannoori、Balaji Seshadri、Hasibur Rahaman、P.N. Arunachalam、Amol G. Dikundwar、Brian E. Fink、Joseph Fargnoli、Mark Fereshteh、Yi Fan、Jonathan Lippy、Ching-Ping Ho、Barri Wautlet、Steven Sheriff、Max Ruzanov、Robert M. Borzilleri

  DOI：10.1016/j.bmc.2018.01.014

  日期：2018.3

  The TGF beta-TGF beta R signaling pathway has been reported to play a protective role in the later stages of tumorigenesis via increasing immunosuppressive Treg cells and facilitating the epithelial to mesenchymal transition (EMT). Therefore, inhibition of TGF beta R has the potential to enhance antitumor immunity. Herein we disclose the identification and optimization of novel heterobicyclic inhibitors of TGF beta RI that demonstrate potent inhibition of SMAD phosphorylation. Application of structure-based drug design to the novel pyrrolotriazine chemotype resulted in improved binding affinity (Ki apparent = 0.14 nM), long residence time (T-1/2 > 120 min) and significantly improved potency in the PSMAD cellular assay (IC50 = 24 nM). Several analogs inhibited phosphorylation of SMAD both in vitro and in vivo. Additionally, inhibition of TGF beta-stimulated phospho-SMAD was observed in primary human T cells. (C) 2018 Elsevier Ltd. All rights reserved.
• Synthesis of non-purine analogs of 6-aryl-9-benzylpurines, and their antimycobacterial activities. Compounds modified in the imidazole ring
  作者：Abhijit Datta Khoje、Aisvareya Kulendrn、Colin Charnock、Baojie Wan、Scott Franzblau、Lise-Lotte Gundersen

  DOI：10.1016/j.bmc.2010.08.016

  日期：2010.10.15

  Purine analogs modified in the five-membered ring have been synthesized and examined for antibacterial activity against Mycobacterium tuberculosis H(37)Rv in vitro employing the microplate alamar blue assay (MABA). The 9-deaza analogs were only found to be weak inhibitors, but the 8-aza-, 7-deaza- and 8-aza-7-deazapurine analogs studied displayed excellent antimycobacterial activities, some even substantially better than the parent purine. In the 7-deazapurine series, MIC values between 0.08 and 0.35 mu M, values comparable or better than the reference drugs used in the study (MIC rifampicin 0.09 mu M, MIC isoniazid 0.28 mu M and MIC PA-824 0.44 mu M). The five most active compounds were also examined against a panel of drug-resistant Mtb strain, and they all retained their activity. The compounds examined were significantly less active against M. tuberculosis in a state of non-replicating persistence (NRP). MIC in the low-oxygen-recovery assay (LORA) >= 60 mu M. The 7-deazapurines were somewhat more toxic towards mammalian cells, but still the selectivity indexes were excellent. The non-purine analogs exhibit a selective antimycobacterial activity. They were essentially inactive against Staphylococcus aureus and Escherichia coli. (C) 2010 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC HYDROXAMIC ACIDS AS PROTEIN DEACETYLASE INHIBITORS AND DUAL PROTEIN DEACETYLASE-PROTEIN KINASE INHIBITORS AND METHODS OF USE THEREOF
  申请人：The Regents of the University of Colorado, a body corporate

  公开号：EP3142652A1

  公开（公告）日：2017-03-22
• Heterocyclic Hydroxamic Acids as Protein Deacetylase Inhibitors and Dual Protein Deacetylase-Protein Kinase Inhibitors and Methods of Use Thereof
  申请人：The Regents of the University of Colorado, A Body Corporate

  公开号：US20170081343A1

  公开（公告）日：2017-03-23

  The present invention relates to novel hydroxamic acids which are specific histone deacetylase (HDAC) inhibitors and/or TTK/Mps1 kinase inhibitors, including pharmaceutically acceptable salts thereof, which are useful for modulating HDAC and/or TTK/Mps1 kinase activity, pharmaceutical compositions comprising these compounds, and processes for their preparation.
• US9840520B2
  申请人：——

  公开号：US9840520B2

  公开（公告）日：2017-12-12