4-氯-6-碘-8-甲基喹啉-3-羧酰胺 | 801315-31-1

• 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
• 中文名称: 4-氯-6-碘-8-甲基喹啉-3-羧酰胺
• 英文名称: 4-chloro-6-iodo-8-methylquinoline-3-carboxamide
• 英文别名: 4-chloro-6-iodo-8-methyl-3-quinolinecarboxamide
• CAS: 801315-31-1
• 化学式: C₁₁H₈ClIN₂O
• 分子量: 346.555
• InChiKey: GFDICSCUTKUVMO-UHFFFAOYSA-N

物化性质

• 沸点：
  465.5±45.0 °C(Predicted)
• 密度：
  1.865±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氯-6-碘-8-甲基喹啉-3-羧酰胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 48.17h， 生成 4-(cyclopentylamino)-8-methyl-6-(3-(oxazol-2-yl)phenyl)quinoline-3-carboxamide
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443
• 作为产物：
  描述：

  4-碘-2-甲基苯胺 在 ammonium hydroxide 、 氯化亚砜 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 二苯醚 、 乙醇 、 水 为溶剂， 反应 4.75h， 生成 4-氯-6-碘-8-甲基喹啉-3-羧酰胺
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443

文献信息

• [EN] QUINOLINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DERIVES DE QUINOLEINE UTILISES EN TANT QU'INHIBITEURS DE LA PHOSPHODIESTERASE
  申请人：GLAXO GROUP LTD

  公开号：WO2004103998A1

  公开（公告）日：2004-12-02

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20 and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了化合物的新结构，其化学式为（I）或其药用盐，其中R1、R2、R19、R20和R34如规范中所述，以及制备这些化合物的方法、含有它们的配方和它们在治疗炎症性疾病中的用途。
• [EN] DERIVATIVES OF 3-AMINOCARBONYLQUINOLINE, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND PROCESSES AND INTERMEDIATES FOR THEIR PREPARATION<br/>[FR] DERIVES DE 3-AMINOCARBONYLQUINOLINE, COMPOSITIONS PHARMACEUTIQUES CONTENANT CES DERIVES ET PROCEDES ET INTERMEDIAIRES SERVANT A LEUR PREPARATION
  申请人：GLAXO GROUP LTD

  公开号：WO2005030725A1

  公开（公告）日：2005-04-07

  Compounds of formula (I) or pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type IV (PDE4) and are of use in the treatment of inflammatory and/or allergic diseases.

  公式(I)的化合物或其药学上可接受的盐是磷酸二酯酶IV型（PDE4）的抑制剂，并可用于治疗炎症和/或过敏性疾病。
• Derivatives of 3-aminocarbonylquinoline, pharmaceutical compositions containing them and processes and intermediates for their preparation
  申请人：Edlin Christopher

  公开号：US20070191426A1

  公开（公告）日：2007-08-16

  Compounds of formula (I) or pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type IV (PDE4) and are of use in the treatment of inflammatory and/or allergic diseases.

  化合物I式或其药学上可接受的盐是磷酸二酯酶IV型（PDE4）的抑制剂，可用于治疗炎症和/或过敏性疾病。
• WO2007/107499
  申请人：——

  公开号：——

  公开（公告）日：——
• DERIVATIVES OF 3-AMINOCARBONYLQUINOLINE, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND PROCESSES AND INTERMEDIATES FOR THEIR PREPARATION
  申请人：GLAXO GROUP LIMITED

  公开号：EP1673345A1

  公开（公告）日：2006-06-28