2-(5-chloropyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone | 1416732-43-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(5-chloropyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone
• 英文别名: 2-(5-Chloropyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone
• CAS: 1416732-43-8
• 化学式: C₁₃H₆ClF₄NO
• 分子量: 303.643
• InChiKey: IMHOABSBBHNKEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(5-chloropyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone 在 potassium carbonate 作用下， 以 乙醚 为溶剂， 生成 1-(5-chloropyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol
  参考文献：
  名称：

  Design and optimization of highly-selective fungal CYP51 inhibitors

  摘要：

  While the orally-active azoles such as voriconazole and itraconazole are effective antifungal agents, they potently inhibit a broad range of off-target human cytochrome P450 enzymes (CYPs) leading to various safety issues (e.g., drug-drug interactions, liver toxicity). Herein, we describe rationally-designed, broad-spectrum antifungal agents that are more selective for the target fungal enzyme, CYP51, than related human CYP enzymes such as CYP3A4. Using proprietary methodology, the triazole metal-binding group found in current clinical agents was replaced with novel, less avid metal-binding groups in concert with potency-enhancing molecular scaffold modifications. This process produced a unique series of fungal CYP51-selective inhibitors that included the oral antifungal 7d (VT-1161), now in Phase 2 clinical trials. This series exhibits excellent potency against key yeast and dermatophyte strains. The chemical methodology described is potentially applicable to the design of new and more effective metalloenzyme inhibitor treatments for a broad array of diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.068
• 作为产物：
  描述：

  2-溴-5-氯吡啶 在 正丁基锂 、 铜 作用下， 以 二甲基亚砜 为溶剂， 生成 2-(5-chloropyridin-2-yl)-1-(2,4-difluorophenyl)-2,2-difluoroethanone
  参考文献：
  名称：

  Design and optimization of highly-selective fungal CYP51 inhibitors

  摘要：

  While the orally-active azoles such as voriconazole and itraconazole are effective antifungal agents, they potently inhibit a broad range of off-target human cytochrome P450 enzymes (CYPs) leading to various safety issues (e.g., drug-drug interactions, liver toxicity). Herein, we describe rationally-designed, broad-spectrum antifungal agents that are more selective for the target fungal enzyme, CYP51, than related human CYP enzymes such as CYP3A4. Using proprietary methodology, the triazole metal-binding group found in current clinical agents was replaced with novel, less avid metal-binding groups in concert with potency-enhancing molecular scaffold modifications. This process produced a unique series of fungal CYP51-selective inhibitors that included the oral antifungal 7d (VT-1161), now in Phase 2 clinical trials. This series exhibits excellent potency against key yeast and dermatophyte strains. The chemical methodology described is potentially applicable to the design of new and more effective metalloenzyme inhibitor treatments for a broad array of diseases. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.068

文献信息

• METALLOENZYME INHIBITOR COMPOUNDS
  申请人：Hoekstra William J.

  公开号：US20130005719A1

  公开（公告）日：2013-01-03

  The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

  本发明描述了具有金属酶调节活性的化合物，以及治疗由这些金属酶介导的疾病、疾病或症状的方法。
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