2-(4-(2-(3-(3-oxo-3-(2-(propylthio)benzo[d]thiazol-6-ylamino)propyl)ureido)ethyl)benzyl)malonic acid | 1370290-32-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-(2-(3-(3-oxo-3-(2-(propylthio)benzo[d]thiazol-6-ylamino)propyl)ureido)ethyl)benzyl)malonic acid
• 英文别名: LDHA Inhibitor, 31；2-[[4-[2-[[3-oxo-3-[(2-propylsulfanyl-1,3-benzothiazol-6-yl)amino]propyl]carbamoylamino]ethyl]phenyl]methyl]propanedioic acid
• CAS: 1370290-32-6
• 化学式: C₂₆H₃₀N₄O₆S₂
• 分子量: 558.679
• InChiKey: XAQKXAUMONXVAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  211
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-氨基-2-巯基苯并噻唑 在 盐酸 、 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 sodium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醚 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 162.0h， 生成 2-(4-(2-(3-(3-oxo-3-(2-(propylthio)benzo[d]thiazol-6-ylamino)propyl)ureido)ethyl)benzyl)malonic acid
  参考文献：
  名称：

  Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

  摘要：

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.

  DOI：

  10.1021/jm201734r

文献信息

• Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation
  作者：Richard A. Ward、Claire Brassington、Alexander L. Breeze、Alessandro Caputo、Susan Critchlow、Gareth Davies、Louise Goodwin、Giles Hassall、Ryan Greenwood、Geoffrey A. Holdgate、Michael Mrosek、Richard A. Norman、Stuart Pearson、Jonathan Tart、Julie A. Tucker、Martin Vogtherr、David Whittaker、Jonathan Wingfield、Jon Winter、Kevin Hudson

  DOI：10.1021/jm201734r

  日期：2012.4.12

  Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate, utilizing NADH as a cofactor. It has been identified as a potential therapeutic target in the area of cancer metabolism. In this manuscript we report our progress using fragment-based lead generation (FBLG), assisted by X-ray crystallography to develop small molecule LDHA inhibitors. Fragment hits were identified through NMR and SPR screening and optimized into lead compounds with nanomolar binding affinities via fragment linking. Also reported is their modification into cellular active compounds suitable for target validation work.