Diethyl 2-[[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]phenyl]methyl]propanedioate | 1370290-38-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Diethyl 2-[[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]phenyl]methyl]propanedioate
• CAS: 1370290-38-2
• 化学式: C₂₁H₃₁NO₇
• 分子量: 409.48
• InChiKey: JXSGQYODRSBUJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Diethyl 2-[[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]phenyl]methyl]propanedioate 在 碳酸氢钠 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 diethyl 2-(4-(2-(3-(3-oxo-3-(2-(propylthio)benzo[d]thiazol-6-ylamino)propyl)ureido)ethoxy)benzyl)malonate
  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
• 作为产物：
  描述：

  N-(叔丁氧羰基)乙醇胺 在 偶氮二甲酸二异丙酯 、 5%-palladium/activated carbon 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 44.0h， 生成 Diethyl 2-[[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]phenyl]methyl]propanedioate
  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.