(S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid | 1152314-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid
• 英文别名: BFF-122；(2S)-6-(4-aminopiperazin-1-yl)-7-fluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• CAS: 1152314-49-2
• 化学式: C₁₇H₁₉FN₄O₄
• 分子量: 362.361
• InChiKey: ICQVSZFWVUBYSI-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  99.3
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N‐nitrosonorlevofloxacin 在 锌 作用下， 生成 (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid
  参考文献：
  名称：

  Crystal Structure-Based Selective Targeting of the Pyridoxal 5′-Phosphate Dependent Enzyme Kynurenine Aminotransferase II for Cognitive Enhancement

  摘要：

  Fluctuations in the brain levels of the neuromodulator kynurenic acid may control cognitive processes and play a causative role in several catastrophic brain diseases. Elimination of the pyridoxal 5'-phosphate dependent enzyme kynurenine aminotransferase II reduces cerebral kynurenic acid synthesis and has procognitive effects. The present description of the crystal structure of human kynurenine aminotransferase II in complex with its potent and specific primary amine-bearing fluoroquinolone inhibitor (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid (BFF-122) should facilitate the structure-based development of cognition-enhancing drugs. From a medicinal chemistry perspective our results demonstrate that the issue of inhibitor specificity for highly conserved PLP-dependent enzymes could be successfully addressed.

  DOI：

  10.1021/jm100464k

文献信息

• KYNURENINE-AMINOTRANSFERASE INHIBITORS
  申请人：University of Maryland, Baltimore

  公开号：EP2222662A2

  公开（公告）日：2010-09-01
• [EN] KYNURENINE-AMINOTRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DE LA KYNURÉNINE-AMINOTRANSFÉRASE
  申请人：UNIV MARYLAND

  公开号：WO2009064836A2

  公开（公告）日：2009-05-22

  Compounds of formula (I) : prodrug derivatives and/or pharmaceutically acceptable salt thereof, selectively inhibit the enzyme kynurenine aminotransferase, thereby reducing the synthesis of kynurenic acid. The compounds are used for the treatment of psychiatric and neurological diseases which benefit from an increase in glutamatergic and/or cholinergic neurotransmission, such as schizophrenia, depression, bipolar illness, anxiety and Alzheimer's disease. Furthermore, the compounds of the invention are useful for stimulating attention, memory and other cognitive processes in normal individuals of any age, including children, adolescents and the elderly. Additionally, the compounds of the invention are also useful for treatment of patients suffering from malaria by preventing parasite gametogenesis and fertility based on reduction of xanthurenic acid formation from its bioprecursor 3 -hydroxy kynurenine.
• Crystal Structure-Based Selective Targeting of the Pyridoxal 5′-Phosphate Dependent Enzyme Kynurenine Aminotransferase II for Cognitive Enhancement
  作者：Franca Rossi、Casazza Valentina、Silvia Garavaglia、Korrapati V. Sathyasaikumar、Robert Schwarcz、Shin-ichi Kojima、Keisuke Okuwaki、Shin-ichiro Ono、Yasushi Kajii、Menico Rizzi

  DOI：10.1021/jm100464k

  日期：2010.8.12

  Fluctuations in the brain levels of the neuromodulator kynurenic acid may control cognitive processes and play a causative role in several catastrophic brain diseases. Elimination of the pyridoxal 5'-phosphate dependent enzyme kynurenine aminotransferase II reduces cerebral kynurenic acid synthesis and has procognitive effects. The present description of the crystal structure of human kynurenine aminotransferase II in complex with its potent and specific primary amine-bearing fluoroquinolone inhibitor (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid (BFF-122) should facilitate the structure-based development of cognition-enhancing drugs. From a medicinal chemistry perspective our results demonstrate that the issue of inhibitor specificity for highly conserved PLP-dependent enzymes could be successfully addressed.