tert-butyl (3S)-3-[({3-[(aminocarbonyl)amino]-5-bromo-2-thienyl}carbonyl)-amino]piperidine-1-carboxylate | 1037743-62-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (3S)-3-[({3-[(aminocarbonyl)amino]-5-bromo-2-thienyl}carbonyl)-amino]piperidine-1-carboxylate
• 英文别名: tert-butyl (3S)-3-[({3-[(aminocarbonyl)amino]-5-bromo-2-thienyl}carbonyl)amino]piperidine-1-carboxylate；tert-butyl (3S)-3-[[5-bromo-3-(carbamoylamino)thiophene-2-carbonyl]amino]piperidine-1-carboxylate
• CAS: 1037743-62-6
• 化学式: C₁₆H₂₃BrN₄O₄S
• 分子量: 447.353
• InChiKey: GLYQMWOQEZVNBR-VIFPVBQESA-N

物化性质

• 沸点：
  545.2±50.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S)-3-[({3-[(aminocarbonyl)amino]-5-bromo-2-thienyl}carbonyl)-amino]piperidine-1-carboxylate 在 盐酸 、 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 5-(4-fluorophenyl)-3-ureidothiophene-2-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
  参考文献：
  名称：

  Discovery of Checkpoint Kinase Inhibitor (S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by Structure-Based Design and Optimization of Thiophenecarboxamide Ureas

  摘要：

  Checkpoint kinases CHK1 and CHK2 are activated in response to DNA damage that results in cell cycle arrest, allowing sufficient time for DNA repair. Agents that lead to abrogation of such checkpoints have potential to increase the efficacy of such compounds as chemo- and radiotherapies. Thiophenecarboxamide ureas (TCUs) were identified as inhibitors of CHK1 by high throughput screening. A structure-based approach is described using crystal structures of JNK1 and CHK1 in complex with 1 and 2 and of the CHK1-3b complex. The ribose binding pocket of CHK1 was targeted to generate inhibitors with excellent cellular potency and selectivity over CDK1 and IKK beta, key features lacking from the initial compounds, Optimization of 3b resulted in the identification of a regioisomeric 3-TCU lead 12a. Optimization of 12a led to the discovery of the clinical candidate 4 (AZD7762), which strongly potentiates the efficacy of a variety of DNA-damaging agents in preclinical models.

  DOI：

  10.1021/jm300025r
• 作为产物：
  描述：

  methyl 5-bromo-3-(3-(2,2,2-trichloroacetyl)-ureido)thiophene-2-carboxylate 在 氨 、 三甲基铝 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 tert-butyl (3S)-3-[({3-[(aminocarbonyl)amino]-5-bromo-2-thienyl}carbonyl)-amino]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Checkpoint Kinase Inhibitor (S)-5-(3-Fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by Structure-Based Design and Optimization of Thiophenecarboxamide Ureas

  摘要：

  Checkpoint kinases CHK1 and CHK2 are activated in response to DNA damage that results in cell cycle arrest, allowing sufficient time for DNA repair. Agents that lead to abrogation of such checkpoints have potential to increase the efficacy of such compounds as chemo- and radiotherapies. Thiophenecarboxamide ureas (TCUs) were identified as inhibitors of CHK1 by high throughput screening. A structure-based approach is described using crystal structures of JNK1 and CHK1 in complex with 1 and 2 and of the CHK1-3b complex. The ribose binding pocket of CHK1 was targeted to generate inhibitors with excellent cellular potency and selectivity over CDK1 and IKK beta, key features lacking from the initial compounds, Optimization of 3b resulted in the identification of a regioisomeric 3-TCU lead 12a. Optimization of 12a led to the discovery of the clinical candidate 4 (AZD7762), which strongly potentiates the efficacy of a variety of DNA-damaging agents in preclinical models.

  DOI：

  10.1021/jm300025r

文献信息

• Thiophene derivatives as chk 1 inhibitors
  申请人：Ashwell Susan

  公开号：US20070010556A1

  公开（公告）日：2007-01-11

  This invention relates to novel compounds having the structural formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment or prophylaxis of cancer.

  本发明涉及具有结构式（I）的新化合物及其制药组合物和使用方法。这些新化合物可用于治疗或预防癌症。
• Thiophene and thiazole derivatives as CHK1 inhibitors
  申请人：AstraZeneca AB

  公开号：EP2305671A1

  公开（公告）日：2011-04-06

  This invention relates to novel compounds having the structural formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment or prophylaxis of cancer.

  本发明涉及具有结构式 (I) 的新型化合物 及其药物组合物和使用方法。这些新型化合物可治疗或预防癌症。
• [EN] THIOPHENE DERIVATIVES AS CHK 1 INIHIBITORS<br/>[FR] HETEROCYCLES SUBSTITUES ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2005066163A3

  公开（公告）日：2005-09-01
• THIOPHENE DERIVATIVES AS CHK 1 INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1732920B1

  公开（公告）日：2011-03-09