[(3R,5S)-5-ethynyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl] morpholine-4-carboxylate | 833473-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: [(3R,5S)-5-ethynyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl] morpholine-4-carboxylate
• CAS: 833473-57-7
• 化学式: C₁₆H₂₄N₂O₅
• 分子量: 324.377
• InChiKey: WOWPRDAEPCYJIP-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(3R,5S)-5-ethynyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl] morpholine-4-carboxylate 、 6-溴-N-(3-氯-4-((3-氟苄基)氧基)苯基)噻吩并[3,2-d]嘧啶-4-胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (3R,5S)-1-(tert-butoxycarbonyl)-5-((4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)thieno[3,2-d]pyrimidin-6-yl)ethynyl)pyrrolidin-3-yl morpholine-4-carboxylate
  参考文献：
  名称：

  Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.11.023

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.
• Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors
  作者：Alex G. Waterson、Kimberly G. Petrov、Keith R. Hornberger、Robert D. Hubbard、Douglas M. Sammond、Stephon C. Smith、Hamilton D. Dickson、Thomas R. Caferro、Kevin W. Hinkle、Kirk L. Stevens、Scott H. Dickerson、David W. Rusnak、Glenn M. Spehar、Edgar R. Wood、Robert J. Griffin、David E. Uehling

  DOI：10.1016/j.bmcl.2009.01.080

  日期：2009.3

  Aniline 'headgroups' were synthesized and incorporated into an alkynyl thienopyrimidine series of EGFR and ErbB-2 inhibitors. Potent inhibition of enzyme activity and cellular proliferation was observed. In certain instances, protein binding was reduced and oral exposure was found to be somewhat improved relative to compounds containing the reference aniline. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSES CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005007083A2

  公开（公告）日：2005-01-27

  The present invention discloses thienopyrimidine derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such thienopyrimidine derivatives are useful in the treatment of diseases associated with inappropriate ErbB family kinase activity.
• 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.