3,5-二甲基-4-氧代-3,4-二氢噻吩并[2,3-d]嘧啶-6-羧酸 | 439138-78-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 中文名称: 3,5-二甲基-4-氧代-3,4-二氢噻吩并[2,3-d]嘧啶-6-羧酸
• 英文名称: 3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid
• 英文别名: 3,5-dimethyl-4-oxothieno[2,3-d]pyrimidine-6-carboxylic acid
• CAS: 439138-78-0
• 化学式: C₉H₈N₂O₃S
• mdl: MFCD02928670
• 分子量: 224.24
• InChiKey: UXEKRAQXZUUDCB-UHFFFAOYSA-N

物化性质

• 沸点：
  484.8±55.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  98.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  哌啶 、 3,5-二甲基-4-氧代-3,4-二氢噻吩并[2,3-d]嘧啶-6-羧酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以64%的产率得到3,5-dimethyl-6-(piperidine-1-carbonyl)thieno[2,3-d]-pyrimidin-4(3H)-one
  参考文献：
  名称：

  Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening

  摘要：

  Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (T-m), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.

  DOI：

  10.1021/acs.jmedchem.5b01607

文献信息

• Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening
  作者：Jennifer A. Borthwick、Nicolas Ancellin、Sophie M. Bertrand、Ryan P. Bingham、Paul S. Carter、Chun-wa Chung、Ian Churcher、Nerina Dodic、Charlène Fournier、Peter L. Francis、Andrew Hobbs、Craig Jamieson、Stephen D. Pickett、Sarah E. Smith、Donald O’N. Somers、Claus Spitzfaden、Colin J. Suckling、Robert J. Young

  DOI：10.1021/acs.jmedchem.5b01607

  日期：2016.3.24

  Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (T-m), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.