6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[2,3-d]pyrimidin-4-amine | 552294-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[2,3-d]pyrimidin-4-amine
• 英文别名: 6-Bromo-N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}thieno[2,3-d]pyrimidin-4-amine；6-bromo-N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]thieno[2,3-d]pyrimidin-4-amine
• CAS: 552294-86-7
• 化学式: C₁₉H₁₂BrClFN₃OS
• 分子量: 464.745
• InChiKey: TYKMVEODBSWVAI-UHFFFAOYSA-N

物化性质

• 沸点：
  592.5±50.0 °C(Predicted)
• 密度：
  1.644±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[2,3-d]pyrimidin-4-amine 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 (4-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-3-methoxyphenyl)methanol
  参考文献：
  名称：

  Identification of fused pyrimidines as interleukin 17 secretion inhibitors

  摘要：

  Inhibiting the interleukin 17 pathway is of interest in a number of autoimmune diseases. Herein, 42 fused pyrimidines have been evaluated as interleukin 17 secretion inhibitors using a phenotypic assay with peripheral blood mononuclear cells. 7H-Pyrrolo [2,3-d]pyrimidin-4-amines having aryl groups at C-S or C-6 were found more active than the corresponding thieno- and furopyrimidines. Low cytotoxicity was seen for the most active inhibitors. However, the pyrrolopyrimidines also inhibit interleukin 5 secretion, suggesting that selective interleukin 17 inhibitors should rather be based on furopyrimidines. Profiling towards a panel of 51 kinases and assays towards the retinoic acid receptor-related orphan receptor gamma were performed in order to identify the compounds mode of action. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.06.019
• 作为产物：
  描述：

  2-氯-4-硝基苯酚 在 potassium carbonate 、 氯化铵 、 锌 作用下， 以 乙醇 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 1.0h， 生成 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery

  摘要：

  Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases, Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzypoxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

  DOI：

  10.1021/acs.jmedchem.5b00515

文献信息

• PROTOZOAN PARASITE GROWTH INHIBITORS
  申请人：Northeastern University

  公开号：US20150259331A1

  公开（公告）日：2015-09-17

  Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be used to inhibit growth of protozoan parasites such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Plasmodium spp.

  用于抑制原生动物寄生虫生长的化合物和方法。通过向主体施用如本文所述的治疗有效量的化合物来治疗原生动物寄生虫感染的方法。这些化合物和方法可用于抑制如非洲锥虫、克鲁兹锥虫、利什曼原虫属和疟原虫属等原生动物寄生虫的生长。
• Evaluation of aromatic 6-substituted thienopyrimidines as scaffolds against parasites that cause trypanosomiasis, leishmaniasis, and malaria
  作者：Jennifer L. Woodring、Gautam Patel、Jessey Erath、Ranjan Behera、Patricia J. Lee、Susan E. Leed、Ana Rodriguez、Richard J. Sciotti、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1039/c4md00441h

  日期：——

  The repurposing of human tyrosine kinase inhibitor scaffolds for generation of antiparasitic agents has provided new lead compounds for tropical diseases.

  人类酪氨酸激酶抑制剂骨架的再利用为生成抗寄生虫药物提供了新的引物化合物，为热带病提供了新的引物化合物。
• Erbb4 co-crystal
  申请人：Shewchuk Marie Lisa

  公开号：US20060134768A1

  公开（公告）日：2006-06-22

  A crystal structure of the ErbB4 kinase domain (ErbB4K), specifically the ErbB4K in liganded form as well as methods of using the same in the discovery of ErbB4 inhibitors. Disclosed further are methods of treatment of diseases mediated by inappropriate ErbB4 activity utilizing ErbB4 inhibitors identified by the methods disclosed herein.

  一种ErbB4激酶结构的晶体结构(ErbB4K)，特别是配体形式下的ErbB4K，以及使用该晶体结构在发现ErbB4抑制剂方面的方法。此外还公开了利用本文所披露的方法确定的ErbB4抑制剂治疗由不适当的ErbB4活性介导的疾病的方法。
• Thienopyrimidine compounds as protein tyrosine kinase inhibitors
  申请人：Caferro R. Thomas

  公开号：US20050009845A1

  公开（公告）日：2005-01-13

  The present invention relates to thienopyrmidine compounds of formula (I) (one of A 1 and A 2 is S and the other is CH), salts thereof, as well as use and preparation of the same. These compounds are inhibitors of various protein tyrosine kinases (PTKs) of the ErbB family and consequently are useful in the treatment of disorders mediated by aberrant activity of such kinases.

  本发明涉及式（I）的噻唑吡啶化合物（其中A1和A2中的一个是S，另一个是CH），其盐，以及其用途和制备方法。这些化合物是ErbB家族的各种蛋白酪氨酸激酶（PTKs）的抑制剂，因此在治疗由这些激酶异常活性介导的疾病方面是有用的。
• Series of Alkynyl-Substituted Thienopyrimidines as Inhibitors of Protozoan Parasite Proliferation
  作者：Jennifer L. Woodring、Ranjan Behera、Amrita Sharma、Justin Wiedeman、Gautam Patel、Baljinder Singh、Paul Guyett、Emanuele Amata、Jessey Erath、Norma Roncal、Erica Penn、Susan E. Leed、Ana Rodriguez、Richard J. Sciotti、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1021/acsmedchemlett.8b00245

  日期：2018.10.11

  Discovery of new chemotherapeutic lead agents can be accelerated by optimizing chemotypes proven to be effective in other diseases to act against parasites. One such medicinal chemistry campaign has focused on optimizing the anilinoquinazoline drug lapatinib (1) and the alkynyl thieno[3,2-d]pyrimidine hit GW837016X (NEU-391, 3) into leads for antitrypanosome drugs. We now report the structure activity relationship studies of 3 and its analogs against Trypanosoma brucei, which causes human African trypanosomiasis (HAT). The series was also tested against Trypanosoma cruzi, Leishmania major, and Plasmodium falciparum. In each case, potent antiparasitic hits with acceptable toxicity margins over mammalian HepG2 and NIH3T3 cell lines were identified. In a mouse model of HAT, 3 extended life of treated mice by 50%, compared to untreated controls. At the cellular level, 3 inhibited mitosis and cytokinesis in T. brucei. Thus, the alkynylthieno[3,2-d]pyrimidine chemotype is an advanced hit worthy of further optimization as a potential chemotherapeutic agent for HAT.