4-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)aniline | 1448807-27-9

• 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-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)aniline
• 英文别名: 4-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)benzenamine；4-Fluoro-3-([1,3]oxazolo[4,5-b]pyridin-2-yl)aniline；4-fluoro-3-([1,3]oxazolo[4,5-b]pyridin-2-yl)aniline
• CAS: 1448807-27-9
• 化学式: C₁₂H₈FN₃O
• 分子量: 229.213
• InChiKey: UOTQQJAPUCXPPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)aniline 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 3.03h， 生成 N-acetyl-N-(4-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)furan-2-carboxamide
  参考文献：
  名称：

  Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

  摘要：

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosorna brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  DOI：

  10.1021/jm401178t
• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 在 tin(II) chloride dihdyrate 作用下， 以 乙酸乙酯 为溶剂， 反应 5.0h， 生成 4-fluoro-3-(oxazolo[4,5-b]pyridin-2-yl)aniline
  参考文献：
  名称：

  Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

  摘要：

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosorna brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  DOI：

  10.1021/jm401178t

文献信息

• 3-(Oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei, the causative agent for human African trypanosomiasis
  作者：Lori Ferrins、Raphaël Rahmani、Melissa L. Sykes、Amy J. Jones、Vicky M. Avery、Eliott Teston、Basmah Almohaywi、JieXiang Yin、Jason Smith、Chris Hyland、Karen L. White、Eileen Ryan、Michael Campbell、Susan A. Charman、Marcel Kaiser、Jonathan B. Baell

  DOI：10.1016/j.ejmech.2013.05.007

  日期：2013.8

  A whole organism high-throughput screen of approximately 87,000 compounds against Trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. Herein we report a structure activity relationship (SAR) investigation around one of these hit classes, the 3-(oxazolo[4,5-b] pyridin-2-yl)anilides. Sharp SAR is revealed, with our most active compound (5) exhibiting an IC50 of 91 nM against the human pathogenic strain T.b. rhodesiense and being more than 700 times less toxic towards the L6 mammalian cell line. Physicochemical properties are attractive for many compounds in this series. For the most potent representatives, we show that solubility and metabolic stability are key parameters to target during future optimisation.[GRAPHICS](C) 2013 Published by Elsevier Masson SAS.