1,1-Dimethylethyl 4-[5-[[(2-bromo-4-thiazolyl)carbonyl]amino]-4-pyrimidinyl]-1-piperazinecarboxylate | 1023299-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1,1-Dimethylethyl 4-[5-[[(2-bromo-4-thiazolyl)carbonyl]amino]-4-pyrimidinyl]-1-piperazinecarboxylate
• 英文别名: tert-butyl 4-[5-[(2-bromo-1,3-thiazole-4-carbonyl)amino]pyrimidin-4-yl]piperazine-1-carboxylate
• CAS: 1023299-30-0
• 化学式: C₁₇H₂₁BrN₆O₃S
• 分子量: 469.362
• InChiKey: JDXCKSDDJVCATK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,1-Dimethylethyl 4-[5-[[(2-bromo-4-thiazolyl)carbonyl]amino]-4-pyrimidinyl]-1-piperazinecarboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.25h， 生成 2-(5-methoxy-3-oxo-1H-isoindol-2-yl)-N-(4-piperazin-1-ylpyrimidin-5-yl)-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors

  摘要：

  Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.108
• 作为产物：
  描述：

  2-溴-4-噻唑羧酸 、 1-[1,1-dimethylethoxycarbonyl]-4-[5-amino-6-pyrimidinyl]piperazine 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 1,1-Dimethylethyl 4-[5-[[(2-bromo-4-thiazolyl)carbonyl]amino]-4-pyrimidinyl]-1-piperazinecarboxylate
  参考文献：
  名称：

  Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors

  摘要：

  Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.108

文献信息

• ANTI-MITOTIC AGENT AND AURORA KINASE INHIBITOR COMBINATION AS ANTI-CANCER TREATMENT
  申请人：Basso-Porcaro Andrea Dawn

  公开号：US20100249030A1

  公开（公告）日：2010-09-30

  The present invention relates to a method of treating cancer by pretreatment with anti-mitotic agents followed by at least one aurora kinase inhibitor. Extensive illustrations are provided for the antimitotic agents and aurora kinase inhibitors that are useful in the inventive treatment.

  本发明涉及一种通过预先使用抗有丝分裂剂，然后再使用至少一种极化素激酶抑制剂来治疗癌症的方法。详细说明了在本发明治疗中有用的抗有丝分裂剂和极化素激酶抑制剂。
• 2-AMINOTHIAZOLE-4-CARBOXYLIC AMIDES AS PROTEIN KINASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2078004B1

  公开（公告）日：2015-02-25
• [EN] ANTI-MITOTIC AGENT AND AURORA KINASE INHIBITOR COMBINATION AS ANTI-CANCER TREATMENT<br/>[FR] COMBINAISON D'AGENT ANTIMITOTIQUE ET D'INHIBITEUR DE L'AURORA KINASE COMME TRAITEMENT ANTI-CANCER
  申请人：SCHERING CORP

  公开号：WO2009017701A2

  公开（公告）日：2009-02-05

  The present invention relates to a method of treating cancer by pretreatment with anti-mitotic agents followed by at least one aurora kinase inhibitor. Extensive illustrations are provided for the antimitotic agents and aurora kinase inhibitors that are useful in the inventive treatment.
• Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors
  作者：Xiaohua Huang、Cliff C. Cheng、Thierry O. Fischmann、José S. Duca、Matthew Richards、Praveen K. Tadikonda、Panduranga Adulla Reddy、Lianyun Zhao、M. Arshad Siddiqui、David Parry、Nicole Davis、Wolfgang Seghezzi、Derek Wiswell、Gerald W. Shipps

  DOI：10.1016/j.bmcl.2013.02.108

  日期：2013.5

  Drug design efforts in the emerging 2-aminothiazole-4-carboxamide class of CHK1 inhibitors have uncovered specific combinations of key substructures within the molecule; resulting in significant improvements in cell-based activity while retaining a greater than one hundred-fold selectivity against CDK2. The X-ray crystal structure of a complex between compound 39 and the CHK1 protein detailing a 'U-shaped' topology and key interactions with the protein surface at the ATP site is also reported. (C) 2013 Elsevier Ltd. All rights reserved.