tert-butyl 5-chloro-N-(diphenylmethylidene)-2-nitro-L-phenylalaninate | 1290617-51-4

• 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: tert-butyl 5-chloro-N-(diphenylmethylidene)-2-nitro-L-phenylalaninate
• 英文别名: tert-butyl (2S)-2-(benzhydrylideneamino)-3-(5-chloro-2-nitrophenyl)propanoate
• CAS: 1290617-51-4
• 化学式: C₂₆H₂₅ClN₂O₄
• 分子量: 464.948
• InChiKey: ALNAHUGLWDFKOY-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  84.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-chloro-N-(diphenylmethylidene)-2-nitro-L-phenylalaninate 在 三氟乙酸 、 盐酸 作用下， 以 二氯甲烷 、 乙醚 、 水 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia

  摘要：

  Kynurenine aminotransferase (KAT) 11 has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT H. An X-ray crystal structure and C-13 NMR studies of PF-04859989 bound to KAT H have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site. In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a brain-penetrant, irreversible inhibitor and is capable of reducing brain kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structure-activity relationship investigations have been completed and have identified the positions on this scaffold best suited to modification for further optimization of this novel series of KAT II inhibitors.

  DOI：

  10.1021/ml200204m
• 作为产物：
  描述：

  2-溴甲基-4-氯-1-硝基苯 、 N-二苯亚甲基-甘氨酸叔丁酯 在 O-烯丙基-N-(9-蒽甲基)溴化金鸡纳碱 、 cesiumhydroxide monohydrate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 tert-butyl 5-chloro-N-(diphenylmethylidene)-2-nitro-L-phenylalaninate
  参考文献：
  名称：

  Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia

  摘要：

  Kynurenine aminotransferase (KAT) 11 has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT H. An X-ray crystal structure and C-13 NMR studies of PF-04859989 bound to KAT H have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site. In vivo pharmacokinetic and efficacy studies in rat show that PF-04859989 is a brain-penetrant, irreversible inhibitor and is capable of reducing brain kynurenic acid by 50% at a dose of 10 mg/kg (sc). Preliminary structure-activity relationship investigations have been completed and have identified the positions on this scaffold best suited to modification for further optimization of this novel series of KAT II inhibitors.

  DOI：

  10.1021/ml200204m

文献信息

• A General Strategy for the Synthesis of Cyclic <i>N</i>-Aryl Hydroxamic Acids via Partial Nitro Group Reduction
  作者：Laura A. McAllister、Bruce M. Bechle、Amy B. Dounay、Edelweiss Evrard、Xinmin Gan、Somraj Ghosh、Ji-Young Kim、Vinod D. Parikh、Jamison B. Tuttle、Patrick R. Verhoest

  DOI：10.1021/jo200530j

  日期：2011.5.6

  We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively

  我们描述了一种通过选择性还原取代的2-硝基苯丙氨酸底物来立体控制取代的环异羟肟酸（3-氨基-1-羟基-3,4-二氢喹啉酮）的一般化方法。该系列化合物具有抗菌特性，最近还被报道为KAT II抑制剂。通过相转移催化的相应硝基苄基溴的烷基化，以优异的产率对映选择性地制备关键的硝基苯基丙氨酸中间体。已经研究了还原环化转化的范围和局限性，并注意了取代方式和电子学对反应效率和副产物形成的影响。此外，