(2S)-2-amino-5-(5-methyl-2-nitrophenylamino)pentanoic acid | 159876-37-6

• 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: (2S)-2-amino-5-(5-methyl-2-nitrophenylamino)pentanoic acid
• 英文别名: (2S)-2-amino-5-(5-methyl-2-nitroanilino)pentanoic acid
• CAS: 159876-37-6
• 化学式: C₁₂H₁₇N₃O₄
• 分子量: 267.285
• InChiKey: VERPLHRIXBHYFT-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-5-(5-methyl-2-nitrophenylamino)pentanoic acid 在 5percent Pd/C 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 22.0h， 生成 (S)-(-)-4-acetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole
  参考文献：
  名称：

  A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates

  摘要：

  A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K-m provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the quinone substrate in the active site resulting in formation of one of the two possible Michael anions resulting from hydride transfer from FADH(2). Electron withdrawing groups on the substrate can stabilize these anions resulting in excellent substrate specificity. Inspection of models indicated that the W-105 and F-106 residues form parallel walls that will accommodate large polycyclic substrates. Thus excellent polycyclic substrates of DT-diaphorase were designed. However, the placement of tetrahedral centers on these polycyclic substrates interfered with the W-105 and the F-106 residues resulting in their exclusion from the active site. The histidine (H194) residue permits recognition of substrate enantiomers as a result of hydrogen bonding interactions. As a result of this study, it will be possible to design poor to excellent substrates of DT-diaphorase and take advantage of varying levels of this enzyme in histologically different cancers.

  DOI：

  10.1021/jm0104365
• 作为产物：
  描述：

  鸟氨酸 、 2-溴-4-甲基-1-硝基苯 在 碳酸氢钠 、 硫化氢 作用下， 以 水 、 丙酮 为溶剂， 反应 3.42h， 以13%的产率得到(2S)-2-amino-5-(5-methyl-2-nitrophenylamino)pentanoic acid
  参考文献：
  名称：

  A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates

  摘要：

  A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K-m provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the quinone substrate in the active site resulting in formation of one of the two possible Michael anions resulting from hydride transfer from FADH(2). Electron withdrawing groups on the substrate can stabilize these anions resulting in excellent substrate specificity. Inspection of models indicated that the W-105 and F-106 residues form parallel walls that will accommodate large polycyclic substrates. Thus excellent polycyclic substrates of DT-diaphorase were designed. However, the placement of tetrahedral centers on these polycyclic substrates interfered with the W-105 and the F-106 residues resulting in their exclusion from the active site. The histidine (H194) residue permits recognition of substrate enantiomers as a result of hydrogen bonding interactions. As a result of this study, it will be possible to design poor to excellent substrates of DT-diaphorase and take advantage of varying levels of this enzyme in histologically different cancers.

  DOI：

  10.1021/jm0104365

文献信息

• 2-nitroaryl and 2-cyanoaryl compounds as regulators of nitric oxide
  申请人：Abbott Laboratories

  公开号：US05362747A1

  公开（公告）日：1994-11-08

  2-Nitroaryl or 2-cyanoaryl compounds of the formula ##STR1## pharmaceutical compositions thereof, intermediates useful in the preparation of these compounds, and methods for treating disorders of vascular smooth muscles or diseases of the cartilage, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, in addition to sickle cell anemia, diabetes, synovitis, chondroarthritis and osteoarthritis by employing these compounds.

  本发明涉及式 ##STR1## 的2-硝基芳基或2-氰基芳基化合物、这些化合物的制备中间体、制药组合物以及使用这些化合物治疗血管平滑肌障碍或软骨、巨噬细胞、神经元、血小板、支气管平滑肌、视肌和胃肠平滑肌的疾病，以及镰状细胞贫血、糖尿病、滑膜炎、软骨关节炎和骨关节炎的方法。
• US5362747A
  申请人：——

  公开号：US5362747A

  公开（公告）日：1994-11-08
• [EN] 2-NITROARYL AND 2-CYANOARYL COMPOUNDS AS REGULATORS OF NITRIC OXIDE SYNTHASE<br/>[FR] COMPOSES 2-NITROARYLE ET 2-CYANOARYLE UTILISES COMME REGULATEURS DE SYNTHASE DE L'OXYDE NITRIQUE
  申请人：——

  公开号：WO1994012163A1

  公开（公告）日：1994-06-09

  [EN] 2-Nitroaryl or 2-cyanoaryl compounds of formula (I), pharmaceutical compositions thereof, intermediates useful in the preparation of these compounds, and methods for treating disorders of vascular smooth muscles or diseases of the cartilage, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, in addition to sickle cell anemia, diabetes, synovitis, chondroarthritis and osteoarthritis by employing these compounds.
  [FR] L'invention se rapporte à des composés 2-nitroaryle ou 2-cyanoaryle de la formule (I), à des compositions pharmaceutiques de ceux-ci, à des intermédiaires utiles dans la préparation de ces composés, et à des procédés visant à traiter les troubles des muscles lisses vasculaires ou les maladies du cartilage, des macrophages, des neurones, des thrombocytes, des muscles lisses bronchiques, des muscles optiques et des muscles lisses gastro-intestinaux, ainsi que la drépanocytose, les diabètes, les synovites, la chondroarthrite et l'ostéoarthrite par l'utilisation de ces composés.
• A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates
  作者：Ali Suleman、Edward B. Skibo

  DOI：10.1021/jm0104365

  日期：2002.3.1

  A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K-m provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the quinone substrate in the active site resulting in formation of one of the two possible Michael anions resulting from hydride transfer from FADH(2). Electron withdrawing groups on the substrate can stabilize these anions resulting in excellent substrate specificity. Inspection of models indicated that the W-105 and F-106 residues form parallel walls that will accommodate large polycyclic substrates. Thus excellent polycyclic substrates of DT-diaphorase were designed. However, the placement of tetrahedral centers on these polycyclic substrates interfered with the W-105 and the F-106 residues resulting in their exclusion from the active site. The histidine (H194) residue permits recognition of substrate enantiomers as a result of hydrogen bonding interactions. As a result of this study, it will be possible to design poor to excellent substrates of DT-diaphorase and take advantage of varying levels of this enzyme in histologically different cancers.