3-methyl-DL-kynurenine | 1446522-57-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-methyl-DL-kynurenine
• 英文别名: 3-methylkynurenine；2-Amino-4-(2-amino-3-methylphenyl)-4-oxobutanoic acid；2-amino-4-(2-amino-3-methylphenyl)-4-oxobutanoic acid
• CAS: 1446522-57-1
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: FESKAFKMBJCZAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-methyl-DL-kynurenine 在 溴 、 sodium acetate 、 溶剂黄146 作用下， 反应 4.0h， 以88%的产率得到(S)-5-chlorokynurenine
  参考文献：
  名称：

  Substrate and inhibitor specificity of kynurenine monooxygenase from Cytophaga hutchinsonii

  摘要：

  Kynurenine monooxygenase (KMO) is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases. We have evaluated substituted kynurenines as substrates or inhibitors of KMO from Cytophaga hutchinsonii. Kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of k(cat) and k(cat)/Km comparable to or higher than kynurenine. However, kynurenines substituted in the 3-position are competitive inhibitors, with K-I values lower than the Km for kynurenine. Bromination also enhances inhibition, and 3,5-dibromokynurenine is a potent competitive inhibitor with a K-1 value of 1.5 mu M. A pharmacophore model of KMO was developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor. The K1 for this compound was found to be 34 mu M, thus validating the pharmacophore model. We are using these results and our model to design more potent inhibitors of KMO. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.02.080
• 作为产物：
  描述：

  ethyl 2-acetamido-2-carboethoxy-5-oxo-5-(2-formamido-3-methylphenyl)pentanoate 在 盐酸 作用下， 以 水 为溶剂， 反应 4.0h， 以75%的产率得到3-methyl-DL-kynurenine
  参考文献：
  名称：

  取代基对智人和荧光假单胞菌犬尿氨酸酶活性的影响

  摘要：

  一系列取代的犬尿氨酸的（3-溴- DL，3-氯DL，3-氟- DL，3-甲基DL，5-溴升，5-氯升，3,5-二溴升和已经合成了5-溴-3-氯-dl），并用人和荧光假单胞菌kynureninase检测了它们的底物活性。检查的所有取代的犬尿氨酸都具有人和荧光假单胞菌犬尿氨酸酶的底物活性。对于人类酶，3-和5取代的犬尿氨酸具有k cat和k cat / K m值高于1- kynurenine，但低于生理底物3-hydroxykynurenine。然而，3，5-二溴-和5-溴-3-氯炔尿氨酸的k cat和k cat / K m值与人炔尿苷酶的3-羟基犬尿氨酸接近。3-卤代取代基对与人犬尿氨酸酶的反应性的影响可能归因于电子效应和/或卤素键。相比之下，对于细菌酶，3-甲基，3-卤代和3,5-二卤代尿嘧啶是较差的底物，而3-氟，5-溴和5-氯炔尿氨酸具有k cat和k cat / K m其生理底物1-

  DOI：

  10.1016/j.bmc.2013.05.039

文献信息

• Substituents effects on activity of kynureninase from Homo sapiens and Pseudomonas fluorescens
  作者：Chandan Maitrani、Robert S. Phillips

  DOI：10.1016/j.bmc.2013.05.039

  日期：2013.8

  5-chloro-l, 3,5-dibromo-l and 5-bromo-3-chloro-dl) have been synthesized and tested for their substrate activity with human and Pseudomonas fluorescens kynureninase. All of the substituted kynurenines examined have substrate activity with both human as well as P. fluorescens kynureninase. For the human enzyme, 3- and 5-substituted kynurenines have kcat and kcat/Km values higher than l-kynurenine, but less

  一系列取代的犬尿氨酸的（3-溴- DL，3-氯DL，3-氟- DL，3-甲基DL，5-溴升，5-氯升，3,5-二溴升和已经合成了5-溴-3-氯-dl），并用人和荧光假单胞菌kynureninase检测了它们的底物活性。检查的所有取代的犬尿氨酸都具有人和荧光假单胞菌犬尿氨酸酶的底物活性。对于人类酶，3-和5取代的犬尿氨酸具有k cat和k cat / K m值高于1- kynurenine，但低于生理底物3-hydroxykynurenine。然而，3，5-二溴-和5-溴-3-氯炔尿氨酸的k cat和k cat / K m值与人炔尿苷酶的3-羟基犬尿氨酸接近。3-卤代取代基对与人犬尿氨酸酶的反应性的影响可能归因于电子效应和/或卤素键。相比之下，对于细菌酶，3-甲基，3-卤代和3,5-二卤代尿嘧啶是较差的底物，而3-氟，5-溴和5-氯炔尿氨酸具有k cat和k cat / K m其生理底物1-
• Substrate and inhibitor specificity of kynurenine monooxygenase from Cytophaga hutchinsonii
  作者：Robert S. Phillips、Andrew D. Anderson、Harvey G. Gentry、Osman F. Güner、J. Phillip Bowen

  DOI：10.1016/j.bmcl.2017.02.080

  日期：2017.4

  Kynurenine monooxygenase (KMO) is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases. We have evaluated substituted kynurenines as substrates or inhibitors of KMO from Cytophaga hutchinsonii. Kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of k(cat) and k(cat)/Km comparable to or higher than kynurenine. However, kynurenines substituted in the 3-position are competitive inhibitors, with K-I values lower than the Km for kynurenine. Bromination also enhances inhibition, and 3,5-dibromokynurenine is a potent competitive inhibitor with a K-1 value of 1.5 mu M. A pharmacophore model of KMO was developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor. The K1 for this compound was found to be 34 mu M, thus validating the pharmacophore model. We are using these results and our model to design more potent inhibitors of KMO. (C) 2017 Elsevier Ltd. All rights reserved.