(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

• 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: (S)-tert-butyl-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidine-1-carboxylate
• 英文别名: NEU-966；tert-butyl (2S)-2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]thieno[3,2-d]pyrimidin-6-yl]ethynyl]pyrrolidine-1-carboxylate
• CAS: 833473-69-1
• 化学式: C₃₀H₂₈ClFN₄O₃S
• 分子量: 579.095
• InChiKey: DCKZXPIZYDMXCT-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(pyrrolidin-2-ylethynyl)thieno[3,2-d]pyrimidin-4-amine
  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：

  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)-2-乙炔-1-吡咯烷羧酸-1,1-二甲基乙酯 在 copper(l) iodide 、 dichlorobis[benzyldiphenylphosphine]palladium(II) 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-tert-butyl-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidine-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

文献信息

• Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines
  作者：Robert D. Hubbard、Scott H. Dickerson、Holly K. Emerson、Robert J. Griffin、Michael J. Reno、Keith R. Hornberger、David W. Rusnak、Edgar R. Wood、David E. Uehling、Alex G. Waterson

  DOI：10.1016/j.bmcl.2008.09.090

  日期：2008.11

  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.
• 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.