4-(imidazol-1-yl)-5-(trifluoromethyl)-1,2-phenylenediamine | 131885-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(imidazol-1-yl)-5-(trifluoromethyl)-1,2-phenylenediamine
• 英文别名: 5-imidazolyl-4-trifluoromethyl-1,2-phenylenediamine；1,2-Benzenediamine, 4-(1H-imidazol-1-yl)-5-(trifluoromethyl)-；4-imidazol-1-yl-5-(trifluoromethyl)benzene-1,2-diamine
• CAS: 131885-99-9
• 化学式: C₁₀H₉F₃N₄
• 分子量: 242.203
• InChiKey: NCAPMCYZEIJMBY-UHFFFAOYSA-N

物化性质

• 沸点：
  421.4±45.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  69.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(imidazol-1-yl)-5-(trifluoromethyl)-1,2-phenylenediamine 在 盐酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 9.5h， 生成
  参考文献：
  名称：

  Design and synthesis of novel 7-heterocycle-6-trifluoromethyl-3-oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group as superior AMPA receptor antagonists with good physicochemical properties

  摘要：

  We describe the design, synthesis, and physicochemical and biological properties of a novel series of 7-heterocycle-6-trifluoromethyl-3-oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group joined through a urethane or urea linkage to the heterocycle at the 7 position. Introduction of the trifluoromethyl group at the 6 position conferred good biological activity, including neuroprotective effects, as well as good physicochemical properties. In terms of alpha-amino-3-hydroxy-5-methylisoxazole propionate receptor (AMPA-R) affinity, a urea linkage was equivalent to a urethane linkage and a pyrrole ring at the 7 position reduced affinity in comparison with an imidazole ring. Among this series, compound 14h (KRP-199), which has a 4-carboxyphenyl group joined through a urethane linkage to a 7-imidazolyl heterocycle, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties, including stability to light and good solubility in aqueous solutions. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.060
• 作为产物：
  描述：

  4-fluoro-3-(trifluoromethyl)acetanilide 在 palladium on activated charcoal 盐酸 、 氢气 、 硝酸 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(imidazol-1-yl)-5-(trifluoromethyl)-1,2-phenylenediamine
  参考文献：
  名称：

  新型的带取代苯基的7-咪唑基-6-三氟甲基喹喔啉羧酸的合成及AMPA受体拮抗活性，并通过引入CF3基团改善了其良好的理化性能。

  摘要：

  我们描述了一系列新的7-咪唑基-6-三氟甲基喹喔啉羧酸的合成，物理化学和生物学特性，这些取代羧酸具有通过C-7位置的氨基甲酸酯键连接的取代苯基。我们发现在C-6位引入三氟甲基带来了良好的生物活性和理化性质。其中，具有4-羧基苯基的化合物9k（KRP-199）在体外具有对AMPA-R的高效力和选择性，并且在体内具有良好的神经保护作用。此外，该化合物表现出良好的理化性质，例如对光的稳定性和在水溶液中的良好溶解性。

  DOI：

  10.1016/j.bmcl.2004.07.093

文献信息

• Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl group and improved its good physicochemical properties by introduced CF3 group
  作者：Yasuo Takano、Futoshi Shiga、Jun Asano、Wataru Hori、Tsuyosi Anraku、Takashi Uno

  DOI：10.1016/j.bmcl.2004.07.093

  日期：2004.10

  We describe the synthesis, physicochemical, and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group attached through a urethane linkage at the C-7 position. We found that the introduction of trifluoromethyl group at the C-6 position brought about good biological activity and physicochemical properties. Among them, compound

  我们描述了一系列新的7-咪唑基-6-三氟甲基喹喔啉羧酸的合成，物理化学和生物学特性，这些取代羧酸具有通过C-7位置的氨基甲酸酯键连接的取代苯基。我们发现在C-6位引入三氟甲基带来了良好的生物活性和理化性质。其中，具有4-羧基苯基的化合物9k（KRP-199）在体外具有对AMPA-R的高效力和选择性，并且在体内具有良好的神经保护作用。此外，该化合物表现出良好的理化性质，例如对光的稳定性和在水溶液中的良好溶解性。
• 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid derivatives, addition salts thereof, and processes for the preparation of both
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US06348461B1

  公开（公告）日：2002-02-19

  The present invention provides 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts, and processes for preparing them, which have antagonism against excitatory amino acid receptors, in particular, an AMPA receptor. The 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts of the present invention are represented by formula (1) wherein Q, R, R1 and R2 are as described in the specification.

  本发明提供了6,7-不对称二取代喹喔啉羧酸化合物及其加合盐，以及制备它们的方法，这些化合物对兴奋性氨基酸受体，特别是AMPA受体具有拮抗作用。本发明的6,7-不对称二取代喹喔啉羧酸化合物及其加合盐由下式表示（1式），其中Q、R、R1和R2如规范中所述。
• Ohmori; Sakamoto; Kubota, Journal of Medicinal Chemistry, 1994, vol. 37, # 4, p. 467 - 475
  作者：Ohmori、Sakamoto、Kubota、Shimizu-Sasamata、Okada、Kawasaki、Hidaka、Togami、Furuya、Murase

  DOI：——

  日期：——
• Cardiotonic agents. Synthesis and cardiovascular properties of novel 2-arylbenzimidazoles and azabenzimidazoles
  作者：Timur Gungor、Andre Fouquet、Jean Marie Teulon、Daniel Provost、Michele Cazes、Alix Cloarec

  DOI：10.1021/jm00101a024

  日期：1992.11

  Novel 2-arylbenzimidazoles and azabenzimidazoles were synthesized, and their inotropic action was evaluated. Changes in left ventricular pressure, dP/dt max, were measured as an index of cardiac contractility. The structural features that impart optimal inotropic activity are presented. The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers. To investigate the mechanism of action, the most potent compounds were tested for their calcium-sensitizing properties and their potential for the inhibition of phosphodiesterase. Two compounds, 1 and 4 1, showed interesting in vitro and oral activity without side effects. They have a more potent calcium-sensitizing effect than MCI-154 and are under futher investigation.
• Design and synthesis of novel 7-heterocycle-6-trifluoromethyl-3-oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group as superior AMPA receptor antagonists with good physicochemical properties
  作者：Yasuo Takano、Futoshi Shiga、Jun Asano、Wataru Hori、Kazunori Fukuchi、Tsuyoshi Anraku、Takashi Uno

  DOI：10.1016/j.bmc.2005.08.060

  日期：2006.2

  We describe the design, synthesis, and physicochemical and biological properties of a novel series of 7-heterocycle-6-trifluoromethyl-3-oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group joined through a urethane or urea linkage to the heterocycle at the 7 position. Introduction of the trifluoromethyl group at the 6 position conferred good biological activity, including neuroprotective effects, as well as good physicochemical properties. In terms of alpha-amino-3-hydroxy-5-methylisoxazole propionate receptor (AMPA-R) affinity, a urea linkage was equivalent to a urethane linkage and a pyrrole ring at the 7 position reduced affinity in comparison with an imidazole ring. Among this series, compound 14h (KRP-199), which has a 4-carboxyphenyl group joined through a urethane linkage to a 7-imidazolyl heterocycle, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties, including stability to light and good solubility in aqueous solutions. (c) 2005 Elsevier Ltd. All rights reserved.