Ethyl 2-amino-5-bromo-6-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]pyridine-3-carboxylate | 1413281-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Ethyl 2-amino-5-bromo-6-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]pyridine-3-carboxylate
• 英文别名: ethyl 2-amino-5-bromo-6-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]pyridine-3-carboxylate
• CAS: 1413281-21-6
• 化学式: C₁₆H₂₂BrN₃O₄
• 分子量: 400.272
• InChiKey: VEVINDRMUVZMAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 2-amino-5-bromo-6-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]pyridine-3-carboxylate 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 2-(二甲基氨基)丙酸 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 生成 Tert-butyl 3-(7-amino-3-bromo-6-carbamoyl-1,8-naphthyridin-2-yl)azetidine-1-carboxylate
  参考文献：
  名称：

  Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity

  摘要：

  A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD+-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1 mg/L) and in vivo anti-staphylococcal activity, is presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.094
• 作为产物：
  描述：

  ethyl 3,3-diaminoacrylate 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 生成 Ethyl 2-amino-5-bromo-6-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]pyridine-3-carboxylate
  参考文献：
  名称：

  Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity

  摘要：

  A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD+-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1 mg/L) and in vivo anti-staphylococcal activity, is presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.094

文献信息

• Structure-guided design, synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-staphylococcal activity
  作者：Jean-Philippe Surivet、Roland Lange、Christian Hubschwerlen、Wolfgang Keck、Jean-Luc Specklin、Daniel Ritz、Daniel Bur、Hans Locher、Peter Seiler、Daniel Stefan Strasser、Lars Prade、Christopher Kohl、Christine Schmitt、Gaëlle Chapoux、Eser Ilhan、Nadia Ekambaram、Alcibiade Athanasiou、Andreja Knezevic、Daniela Sabato、Alain Chambovey、Mika Gaertner、Michel Enderlin、Maria Boehme、Virginie Sippel、Pierre Wyss

  DOI：10.1016/j.bmcl.2012.08.094

  日期：2012.11

  A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent inhibition of bacterial NAD+-dependent DNA ligases (LigAs) evolved from a 2,4-diaminopteridine derivative discovered by HTS. The design was guided by several highly resolved X-ray structures of our inhibitors in complex with either Streptococcus pneumoniae or Escherichia coli LigA. The structure-activity-relationship based on the ANC scaffold is discussed. The in-depth characterization of 2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which displayed promising in vitro (MIC Staphylococcus aureus 1 mg/L) and in vivo anti-staphylococcal activity, is presented. (C) 2012 Elsevier Ltd. All rights reserved.