tert-butyl (2S,4R)-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)-4-((ethoxycarbonyl)amino)pyrrolidine-1-carboxylate | 1093230-04-6

• 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: tert-butyl (2S,4R)-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)-4-((ethoxycarbonyl)amino)pyrrolidine-1-carboxylate
• CAS: 1093230-04-6
• 化学式: C₃₃H₃₃ClFN₅O₅S
• 分子量: 666.173
• InChiKey: JWDYBOHJFHDBOE-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.28
• 重原子数：
  46.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  114.91
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4R)-2-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)-4-((ethoxycarbonyl)amino)pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 ethyl (3R,5S)-5-((4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidin-3-ylcarbamate
  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 、 tert-butyl (2S,4R)-4-((ethoxycarbonyl)amino)-2-ethynylpyrrolidine-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-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)-4-((ethoxycarbonyl)amino)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

• Application of a trifunctional reactive linker for the construction of antibody–drug hybrid conjugates
  作者：Joshua D. Thomas、Thomas Hofer、Christoph Rader、Terrence R. Burke

  DOI：10.1016/j.bmcl.2008.09.078

  日期：2008.11

  A flexible, trifunctional poly(ethylene glycol)-succinamide-Lysine-Lysine-maleimide (PEG-SU-Lys-Lysmal) linker was employed to simultaneously allow biotin tagging and cell-surface targeting through an integrin alpha(4)beta(1)-binding peptidomimetic that was regiospecifically conjugated to an IgG1-derived Fc fragment with an engineered C-terminal selenocysteine residue. The resulting antibody derivative mediates Fc receptor binding by virtue of the Fc protein and selectively targets cancer cells expressing human integrin alpha(4)beta(1). The PEG-SU-Lys-Lys-mal linker may have general utility as an organic tether for the construction of antibody-drug conjugates. (C) 2008 Elsevier Ltd. All rights reserved.