5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)isoindolin-1-one | 944807-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)isoindolin-1-one
• 英文别名: (S)-5-(2-(2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)isoindolin-1-one；5-[2-[[(2S)-2-amino-3-[4-(trifluoromethyl)phenyl]propyl]amino]-1,3-thiazol-5-yl]-2,3-dihydroisoindol-1-one
• CAS: 944807-01-6
• 化学式: C₂₁H₁₉F₃N₄OS
• 分子量: 432.469
• InChiKey: UFEUMFPFVBUZRR-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 生成 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)isoindolin-1-one
  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 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。
• 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
• [EN] THIAZOLE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES THIAZOLE ET PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2007084391A2

  公开（公告）日：2007-07-26

  [EN] 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.
  [FR] La présente invention concerne des composés thiazole de formule (I) et formule (II), ainsi que des compositions les comprenant utiles pour traiter les maladies liées à l'activité de la protéine kinase B (PKB). Dans ces formules, les variables sont telles que définies dans la description. L'invention concerne également l'utilisation thérapeutique desdits composés thiazole et de compositions les contenant pour le traitement d'états maladifs associés à la prolifération anormale des cellules, aux cancers, aux inflammations et aux troubles métaboliques.