ethyl 4-benzoyl-3-methyl-2-butenoate | 82343-51-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-benzoyl-3-methyl-2-butenoate
• 英文别名: ethyl 3-methyl-5-oxo-5-phenyl-2-pentenoate；Ethyl 3-methyl-5-oxo-5-phenylpent-2-enoate；ethyl 3-methyl-5-oxo-5-phenylpent-2-enoate
• CAS: 82343-51-9
• 化学式: C₁₄H₁₆O₃
• 分子量: 232.279
• InChiKey: NYYZQVCVQFHONW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-benzoyl-3-methyl-2-butenoate 在 硫酸 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 生成 4-methyl-6-phenyl-2H-pyran-2-one
  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：

  3-甲基-2-丁烯酸乙酯 、 苯甲酰氯 在 aluminum (III) chloride 作用下， 反应 5.0h， 生成 ethyl 4-benzoyl-3-methyl-2-butenoate
  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

文献信息

• Carbon–carbon bond formation at the γ-position of dienolates via the palladium catalysed coupling of the tin masked dienolates
  作者：Yoshinori Yamamoto、Satoshi Hatsuya、Jun-Ichi Yamada

  DOI：10.1039/c39880000086

  日期：——

  The palladium catalysed coupling reaction of the tin masked dienolate (2) with organic halides takes place at the position substituted by thin, thereby providing a new method for C–C bond formation at the γ-position of dienolates.

  锡掩蔽的二烯酸酯（2）与有机卤化物的钯催化偶联反应发生在被薄取代的位置，从而为二烯酸酯的γ-位形成C-C键提供了一种新方法。
• Stabilization and activation of dienolates with germanium and tin. Stereo- and regioselective aldol reactions, regioselective coupling reactions, and regioselective synthesis of amino acid derivatives
  作者：Yoshinori Yamamoto、Satoshi Hatsuya、Junichi Yamada

  DOI：10.1021/jo00297a030

  日期：1990.5
• Selective .gamma.-substitution of .alpha.,.beta.-unsaturated esters via .alpha.-trimethylsilyl .beta.,.gamma.-unsaturated esters
  作者：Pamela Albaugh-Robertson、John A. Katzenellenbogen

  DOI：10.1021/jo00174a026

  日期：1983.12
• Silicon-directed selective gamma substitution of an α,β-unsaturated ester
  作者：Pamela Albaugh-Robertson、John A. Katzenellenbogen

  DOI：10.1016/s0040-4039(00)86931-2

  日期：1982.1
• Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase
  作者：Baisong Zheng、Yuan Yao、Zhen Liu、Lisheng Deng、Justin L. Anglin、Hong Jiang、B. V. Venkataram Prasad、Yongcheng Song

  DOI：10.1021/ml400036z

  日期：2013.6.13

  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.