6-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺 | 552295-33-7

• 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
• 中文名称: 6-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺
• 英文名称: 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[3,2-d]pyrimidin-4-amine
• 英文别名: 6-bromo-N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]thieno[3,2-d]pyrimidin-4-amine
• CAS: 552295-33-7
• 化学式: C₁₉H₁₂BrClFN₃OS
• 分子量: 464.745
• InChiKey: GXPTWTGUCGOQOY-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)：
  6.4
• 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

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(thiophen-2-yl)thieno[3,2-d]pyrimidin-4-amine	1135150-70-7	C23H15ClFN3OS2	467.975
  ——	(S)-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(pyrrolidin-2-ylethynyl)thieno[3,2-d]pyrimidin-4-amine	833473-68-0	C25H20ClFN4OS	478.977
  ——	N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-(furan-2-yl)thieno[3,2-d]pyrimidin-4-amine	1135150-63-8	C23H15ClFN3O2S	451.908
  ——	N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(3-morpholinophenyl)thieno[3,2-d]pyrimidin-4-amine	——	C29H24ClFN4O2S	547.053
  ——	(S)-tert-butyl-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidine-1-carboxylate	833473-69-1	C30H28ClFN4O3S	579.095
  ——	E-tert-butyl (2R)-2-{[4-({3-chloro-4-[(3-fluorobenzyl) oxy] phenyl} amino) thieno[3,2-d]pyrimidin-6-yl] ethynyl} pyrrolidine-1-carboxylate	833473-71-5	C30H28ClFN4O3S	579.095
  ——	tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-(ethylcarbamoyloxy)pyrrolidine-1-carboxylate	833473-61-3	C33H33ClFN5O5S	666.173

反应信息

• 作为反应物：
  描述：

  6-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺 、 (2S,4R)-tert-butyl 2-ethynyl-4-hydroxypyrrolidine-1-carboxylate 在 copper(l) iodide 、 dichlorobis[benzyldiphenylphosphine]palladium(II) 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (2S,4R)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]-4-hydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

  摘要：

  A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d] pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modi. cation of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.090
• 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-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺
  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。
• Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors
  作者：Kirk L. Stevens、Krystal J. Alligood、Jennifer G. Badiang Alberti、Thomas R. Caferro、Stanley D. Chamberlain、Scott H. Dickerson、Hamilton D. Dickson、Holly K. Emerson、Robert J. Griffin、Robert D. Hubbard、Barry R. Keith、Robert J. Mullin、Kimberly G. Petrov、Roseanne M. Gerding、Michael J. Reno、Tara R. Rheault、David W. Rusnak、Douglas M. Sammond、Stephon C. Smith、David E. Uehling、Alex G. Waterson、Edgar R. Wood

  DOI：10.1016/j.bmcl.2008.11.023

  日期：2009.1

  A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.
• Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors
  作者：Tara R. Rheault、Thomas R. Caferro、Scott H. Dickerson、Kelly H. Donaldson、Michael D. Gaul、Aaron S. Goetz、Robert J. Mullin、Octerloney B. McDonald、Kimberly G. Petrov、David W. Rusnak、Lisa M. Shewchuk、Glenn M. Spehar、Anne T. Truesdale、Dana E. Vanderwall、Edgar R. Wood、David E. Uehling

  DOI：10.1016/j.bmcl.2008.12.011

  日期：2009.2

  Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative activity with IC50 values less than 1 mu M against human tumor cells in vitro. (C) 2008 Elsevier Ltd. All rights reserved.