4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-(methyloxy)-1H-imidazole-5-carboxamide | 1093259-88-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-(methyloxy)-1H-imidazole-5-carboxamide
• 英文别名: 5-chloro-N-[[4-chloro-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]methyl]-2-methoxy-1H-imidazole-4-carboxamide
• CAS: 1093259-88-1
• 化学式: C₁₉H₁₂Cl₃FN₄O₃
• 分子量: 469.687
• InChiKey: VFMKKEGDCATBTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-(methyloxy)-1H-imidazole-5-carboxamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 194.0h， 以15%的产率得到5-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  Rational Design of Potent Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

  摘要：

  A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50 < 1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.

  DOI：

  10.1021/jm301294g
• 作为产物：
  描述：

  {3-[(3-chloro-5-cyanophenyl)oxy]-2-fluoro-4-nitrophenyl}acetic acid 在 copper(I) oxide 、 N-溴代丁二酰亚胺(NBS) 、 亚硝酸特丁酯 、 sodium dithionite 、 偶氮二异丁腈 、 氨 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 copper dichloride 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.5h， 生成 4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-2-(methyloxy)-1H-imidazole-5-carboxamide
  参考文献：
  名称：

  Rational Design of Potent Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

  摘要：

  A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50 < 1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.

  DOI：

  10.1021/jm301294g

文献信息

• Chemical compounds
  申请人：GlaxoSmithKline LLC

  公开号：US08304419B2

  公开（公告）日：2012-11-06

  The present invention relates to compounds that are a non-nucleoside reverse transcriptase inhibitors, and to processes for the preparation and use of the same. Specifically, the present invention includes methods of using such compounds in the treatment of human immunodeficiency virus infection.

  本发明涉及一种非核苷类逆转录酶抑制剂化合物，以及制备和使用该化合物的方法。具体而言，本发明涉及使用这些化合物治疗人类免疫缺陷病毒感染的方法。
• CHEMICAL COMPOUNDS
  申请人：GlaxoSmithKline LLC

  公开号：EP2166856A1

  公开（公告）日：2010-03-31
• US8304419B2
  申请人：——

  公开号：US8304419B2

  公开（公告）日：2012-11-06
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008154271A1

  公开（公告）日：2008-12-18

  [EN] The present invention relates to compounds that are a non-nucleoside reverse transcriptase inhibitors, and to processes for the preparation and use of the same. Specifically, the present invention includes methods of using such compounds in the treatment of human immunodeficiency virus infection.
  [FR] La présente invention concerne des composés qui sont des inhibiteurs non nucléosidiques de la transcriptase inverse, et des procédés pour leur préparation et leur utilisation. De manière spécifique, la présente invention comprend des procédés d'utilisation de tels composés dans le traitement de l'infection par le virus d'immunodéficience humaine.