diethyl acetamido-(2-amino-5-ethylphenacyl)-malonate | 164788-97-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl acetamido-(2-amino-5-ethylphenacyl)-malonate
• 英文别名: Diethyl 2-acetamido-2-[2-(2-amino-5-ethylphenyl)-2-oxoethyl]propanedioate
• CAS: 164788-97-0
• 化学式: C₁₉H₂₆N₂O₆
• 分子量: 378.425
• InChiKey: PVESMRNKNVQBBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl acetamido-(2-amino-5-ethylphenacyl)-malonate 在 盐酸 作用下， 反应 6.0h， 以95%的产率得到(D,L)-5-ethylkynurenine
  参考文献：
  名称：

  Derivatives of kynurenine as inhibitors of rat brain kynurenine aminotransferase

  摘要：

  The structural requirements of the catalytic site of kynurenine aminotransferase (KAT), the enzyme responsible for the conversion of L-kynurenine (KYN) to kynurenic acid (KYNA), were examined using analogs and derivatives of KYN: KYNA production from KYN was monitored in rat brain homogenates and brain tissue slices. Modification of KYN's acylalanine side chain or its ring amino group resulted in compounds which did not substantially affect KYNA synthesis. Ring chlorination in positions 3, 4, 5 and 6 yielded KYN analogs which interfered with KYNA production. L-5-Cl-KYN was the most active of the chlorinated kynurenines, and one of the most potent of several other 5-substituted kynurenines. L-5-Cl-KYN was an excellent substrate of KAT, yielding 6-Cl-KYNA. Finally, in kinetic studies, L-5-Cl-KYN (K-i = 5.4 mu M) was found to have an approximately five times higher affinity to the enzyme than the natural substrate KYN (K-m = 28 mu M).

  DOI：

  10.1016/s0223-5234(96)80002-x
• 作为产物：
  描述：

  4-乙基苯胺 在 三氯化铝 、 sodium 、 三氯化硼 作用下， 反应 45.0h， 生成 diethyl acetamido-(2-amino-5-ethylphenacyl)-malonate
  参考文献：
  名称：

  Derivatives of kynurenine as inhibitors of rat brain kynurenine aminotransferase

  摘要：

  The structural requirements of the catalytic site of kynurenine aminotransferase (KAT), the enzyme responsible for the conversion of L-kynurenine (KYN) to kynurenic acid (KYNA), were examined using analogs and derivatives of KYN: KYNA production from KYN was monitored in rat brain homogenates and brain tissue slices. Modification of KYN's acylalanine side chain or its ring amino group resulted in compounds which did not substantially affect KYNA synthesis. Ring chlorination in positions 3, 4, 5 and 6 yielded KYN analogs which interfered with KYNA production. L-5-Cl-KYN was the most active of the chlorinated kynurenines, and one of the most potent of several other 5-substituted kynurenines. L-5-Cl-KYN was an excellent substrate of KAT, yielding 6-Cl-KYNA. Finally, in kinetic studies, L-5-Cl-KYN (K-i = 5.4 mu M) was found to have an approximately five times higher affinity to the enzyme than the natural substrate KYN (K-m = 28 mu M).

  DOI：

  10.1016/s0223-5234(96)80002-x

文献信息

• Substituted kynurenines, a process for their preparation, and use as medicaments
  申请人：THE UNIVERSITY OF MARYLAND AT BALTIMORE

  公开号：EP0919538A1

  公开（公告）日：1999-06-02

  The present invention relates to the use in the treatment of cognitive disorders associted with the aging processes of the brain and perinatal brain disorders of compounds which act as inhibitors of the enzyme kynurenine aminotransferase (KAT). The present invention also provides, as novel compounds, a selected class of KAT inhibitors which are the compounds of formula (IA), wherein R is halogen, C1-C6 alkyl, C5-C7 cycloalkyl, phenyl-C1-C4 alkyl, C1-C6 alkoxy, C6-C10 aryloxy, phenyl-C1-C4 alkoxy or trifluoromethyl, and R1 is hydroxy, C1-C6 alkoxy, amino, mono-C1-C6 alkylamino di-C1-C6 alkylamino, hydroxylamino, C1-C4 alkoxyamino or benzyloxyamino, with the provisos that: (i) when R1 is hydroxy and at the same time, R is halogen, then this halogen is not fluorine; and (ii) when R1 is hydroxy and, at the same time, R is C1-C6 alkyl, then this C1-C6 alkyl is not methyl, either as a single isomer or as a mixture of isomers, and the pharmaceutically acceptable salts thereof.

  本发明涉及作为犬尿氨酸氨基转移酶（KAT）抑制剂的化合物在治疗与大脑衰老过程有关的认知障碍和围产期大脑障碍中的应用。C6-C10芳氧基、苯基-C1-C4 烷氧基或三氟甲基，而 R1 是羟基、C1-C6 烷氧基、氨基、单-C1-C6 烷基氨基、二-C1-C6 烷基氨基、羟基氨基、C1-C4 烷氧基氨基或苄氧基氨基，但前提是(i) 当 R1 是羟基，同时 R 是卤素时，该卤素不是氟；以及 (ii) 当 R1 是羟基，同时 R 是 C1-C6 烷基时，该 C1-C6 烷基不是甲基，可以是单一异构体，也可以是异构体的混合物，以及它们的药学上可接受的盐。
• SUBSTITUTED KYNURENINES, A PROCESS FOR THEIR PREPARATION, AND USE AS MEDICAMENTS
  申请人：THE UNIVERSITY OF MARYLAND AT BALTIMORE

  公开号：EP0663899A1

  公开（公告）日：1995-07-26
• EP0663899A4
  申请人：——

  公开号：EP0663899A4

  公开（公告）日：1996-01-17
• US5519055A
  申请人：——

  公开号：US5519055A

  公开（公告）日：1996-05-21
• US5708030A
  申请人：——

  公开号：US5708030A

  公开（公告）日：1998-01-13