tert-butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide | 944805-79-2

• 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: tert-butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide
• 英文别名: tert-butyl 4-((S)-1-(4-(trifluoromethyl)phenyl)methyl)-1,2,3-oxathiazolidine-3-carboxylate, 2,2-dioxide；(S)-tert-butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide；(S)-tert-butyl-4-(4-trifluoromethylbenzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide；tert-butyl (4S)-2,2-dioxo-4-[[4-(trifluoromethyl)phenyl]methyl]oxathiazolidine-3-carboxylate
• CAS: 944805-79-2
• 化学式: C₁₅H₁₈F₃NO₅S
• 分子量: 381.373
• InChiKey: NASHXMFMSHZCQF-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (R,S)-tert-butyl-(S)-4-(4-trifluoromethylbenzyl)-1,2,3-oxathiazolidine-3-carboxylate-2-oxide 在 ruthenium trichloride 、 sodium periodate 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 18.0h， 以97%的产率得到tert-butyl (4S)-4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide
  参考文献：
  名称：

  [EN] FLUOROISOQUINOLINE SUBSTITUTED THIAZOLE COMPOUNDS AND METHODS OF USE
  [FR] THIAZOLES SUBSTITUÉS PAR FLUOROISOQUINOLÉINE ET LEURS MÉTHODES D'APPLICATION

  摘要：

  该发明涉及式(I)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使用这种噻唑化合物和其组合物的治疗用途。

  公开号：

  WO2010083246A1

文献信息

• 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。
• Heterocyclic modulators of PKB
  申请人：ZENG Qingping

  公开号：US20090275592A1

  公开（公告）日：2009-11-05

  The invention relates to heterocyclic compounds of Formula I 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 compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种公式I的杂环化合物及其组合物，其中变量具有本文所提供的定义，其在治疗由蛋白激酶B（PKB）介导的疾病方面具有用途。本发明还涉及这种化合物和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方面的治疗用途。
• Thiadiazole modulators of PKB
  申请人：Zeng Qingping

  公开号：US20090298836A1

  公开（公告）日：2009-12-03

  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.

  本发明涉及一种化合物，其为公式I和公式II的噻唑化合物，以及其组合物，可用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有本文中提供的定义。本发明还涉及在治疗异常细胞生长、癌症、炎症和代谢紊乱等疾病状态中使用这种噻唑化合物和其组合物的治疗用途。
• FLUOROISOQUINOLINE SUBSTITUTED THIAZOLE COMPOUNDS AND METHODS OF USE
  申请人：Zeng Qingping

  公开号：US20110263647A1

  公开（公告）日：2011-10-27

  The invention relates to thiazole compounds of Formula I 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.

  本发明涉及一种式I的噻唑化合物及其组合物，其在治疗由蛋白激酶B（PKB）介导的疾病方面具有用途，其中变量具有本文所提供的定义。本发明还涉及在治疗与异常细胞生长、癌症、炎症和代谢紊乱有关的疾病状态中使用此类噻唑化合物和其组合物的治疗用途。
• [EN] HETEROCYCLIC MODULATORS OF PKB<br/>[FR] MODULATEURS HÉTÉROCYCLIQUES DE PKB
  申请人：AMGEN INC

  公开号：WO2009011880A3

  公开（公告）日：2009-04-02