(S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate | 944804-72-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate
• 英文别名: (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate；tert-butyl N-(5-bromo-1,3-thiazol-2-yl)-N-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-(trifluoromethyl)phenyl]propyl]carbamate
• CAS: 944804-72-2
• 化学式: C₂₃H₂₉BrF₃N₃O₄S
• 分子量: 580.466
• InChiKey: BQEYXLQBLMWOCS-INIZCTEOSA-N

物化性质

• 密度：
  1.387±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-氰基-2-氟苯硼酸频哪醇酯 、 (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.34h， 生成 tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate
  参考文献：
  名称：

  Thiazole compounds and methods of use

  摘要：

  该发明涉及Formula I和Formula II的噻唑化合物及其组合物，用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有此处提供的定义。该发明还涉及这种噻唑化合物及其组合物在治疗与异常细胞生长、癌症、炎症和代谢紊乱相关的疾病状态中的治疗用途。

  公开号：

  US20070173506A1
• 作为产物：
  描述：

  tert-butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide 、 N-BOC-2-氨基-5-溴噻唑 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate
  参考文献：
  名称：

  Azole-based inhibitors of AKT/PKB for the treatment of cancer

  摘要：

  Through a combination of screening and structure-based rational design, we have discovered a series of N-1-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.067

文献信息

• THIAZOLE COMPOUNDS AS PROTEIN KINASE B (PKB) INHIBITORS
  申请人：Amgen, Inc

  公开号：EP1981884B1

  公开（公告）日：2012-06-13
• US7514566B2
  申请人：——

  公开号：US7514566B2

  公开（公告）日：2009-04-07
• US8084479B2
  申请人：——

  公开号：US8084479B2

  公开（公告）日：2011-12-27
• Thiazole compounds and methods of use
  申请人：Zeng Qingping

  公开号：US20070173506A1

  公开（公告）日：2007-07-26

  The invention relates to thiazole compounds of Formula I and Formula II and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  该发明涉及Formula I和Formula II的噻唑化合物及其组合物，用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有此处提供的定义。该发明还涉及这种噻唑化合物及其组合物在治疗与异常细胞生长、癌症、炎症和代谢紊乱相关的疾病状态中的治疗用途。
• Azole-based inhibitors of AKT/PKB for the treatment of cancer
  作者：Qingping Zeng、John G. Allen、Matthew P. Bourbeau、Xianghong Wang、Guomin Yao、Seifu Tadesse、James T. Rider、Chester C. Yuan、Fang-Tsao Hong、Matthew R. Lee、Shiwen Zhang、Julie A. Lofgren、Daniel J. Freeman、Suijin Yang、Chun Li、Elizabeth Tominey、Xin Huang、Douglas Hoffman、Harvey K. Yamane、Christopher Fotsch、Celia Dominguez、Randall Hungate、Xiaoling Zhang

  DOI：10.1016/j.bmcl.2010.01.067

  日期：2010.3

  Through a combination of screening and structure-based rational design, we have discovered a series of N-1-(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma. (C) 2010 Elsevier Ltd. All rights reserved.