| 1434047-50-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 1434047-50-3
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: RPOMRIAZCYXCLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.21
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  42.35
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  在 10 wt% Pd(OH)2 on carbon 作用下， 以 乙酸乙酯 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase

  摘要：

  Mutations in isocitrate dehydrogenase (IDH), a key enzyme in the tricarboxylic acid cycle, have recently been found in similar to 75% glioma and similar to 20% acute myeloid leukemia. Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. Strong evidence has shown mutant IDH1 represents a novel target for this type of cancer. We found two 1-hydroxypyridin-2-one compounds that are potent inhibitors of R132H and R132C mutants with K-i values as low as 120 nM. These compounds exhibit >60-fold selectivity against wild-type IDH1 and can inhibit the production of D-2-hydroxyglutaric acid in IDH1 mutated cells, representing novel chemical Probes for cancer biology studies. We also report the first inhibitor-bound crystal structures of IDH1(R132H), showing these inhibitors have H-bond, electrostatic, and hydrophobic interactions with the mutant enzyme. Comparison with the substrate-bound IDH1 structures revealed the structural basis for the high enzyme selectivity of these compounds.

  DOI：

  10.1021/ml400036z
• 作为产物：
  描述：

  柠嗪酸 在 正丁基锂 、 四甲基乙二胺 、 三乙胺 、 三溴氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 57.0h， 生成
  参考文献：
  名称：

  Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase

  摘要：

  Mutations in isocitrate dehydrogenase (IDH), a key enzyme in the tricarboxylic acid cycle, have recently been found in similar to 75% glioma and similar to 20% acute myeloid leukemia. Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. Strong evidence has shown mutant IDH1 represents a novel target for this type of cancer. We found two 1-hydroxypyridin-2-one compounds that are potent inhibitors of R132H and R132C mutants with K-i values as low as 120 nM. These compounds exhibit >60-fold selectivity against wild-type IDH1 and can inhibit the production of D-2-hydroxyglutaric acid in IDH1 mutated cells, representing novel chemical Probes for cancer biology studies. We also report the first inhibitor-bound crystal structures of IDH1(R132H), showing these inhibitors have H-bond, electrostatic, and hydrophobic interactions with the mutant enzyme. Comparison with the substrate-bound IDH1 structures revealed the structural basis for the high enzyme selectivity of these compounds.

  DOI：

  10.1021/ml400036z