(S)-N-(1-azido-3-(2,4-dichlorophenyl)propan-2-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole-5-carboxamide | 1261080-73-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (S)-N-(1-azido-3-(2,4-dichlorophenyl)propan-2-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole-5-carboxamide
• 英文别名: N-[(2S)-1-azido-3-(2,4-dichlorophenyl)propan-2-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,3-thiazole-5-carboxamide
• CAS: 1261080-73-2
• 化学式: C₂₀H₁₅Cl₂N₇OS
• 分子量: 472.357
• InChiKey: DNEGPUOTTVFXCO-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-N-(1-azido-3-(2,4-dichlorophenyl)propan-2-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole-5-carboxamide 在 palladium 10% on activated carbon 、 氢气 作用下， 反应 5.0h， 以78%的产率得到(S)-N-(1-amino-3-(2,4-dichlorophenyl)propan-2-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole-5-carboxamide
  参考文献：
  名称：

  New thiazole carboxamides as potent inhibitors of Akt kinases

  摘要：

  A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)-2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3 beta proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.080
• 作为产物：
  描述：

  4-溴-7-氮杂吲哚 在 四(三苯基膦)钯 、 bis[1,2-bis(diphenylphosphino)ferrocene]-palladium(0) 、 水 、 potassium acetate 、 sodium hydride 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.17h， 生成 (S)-N-(1-azido-3-(2,4-dichlorophenyl)propan-2-yl)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiazole-5-carboxamide
  参考文献：
  名称：

  New thiazole carboxamides as potent inhibitors of Akt kinases

  摘要：

  A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)-2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3 beta proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.080

文献信息

• 5-噻唑酰胺类化合物及生物学应用
  申请人：中山大学肿瘤防治中心

  公开号：CN101921268B

  公开（公告）日：2016-08-03

  本发明涉及一种5?噻唑酰胺类化合物及生物学应用，其结构式为本发明提供了由通式(I)表示的靶向AKT/PKB激酶(ATP结合位点)的5?噻唑酰胺类化合物。实验证明，本发明所涉及的噻唑酰胺类AKT抑制剂能在体外显著抑制AKT激酶的活性，并对多种AKT活性高的肿瘤细胞株具有很强的增殖抑制作用，表明噻唑酰胺类化合物可用于制备抗肿瘤药物。