ethyl 2-[4-[2-(tert-butoxycarbonylamino)ethylamino]cyclohexyl]acetate | 1613269-84-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 2-[4-[2-(tert-butoxycarbonylamino)ethylamino]cyclohexyl]acetate
• 英文别名: ethyl 2-(trans-4-((2-((tert-butoxycarbonyl)amino)ethyl)amino)cyclohexyl)acetate
• CAS: 1613269-84-3
• 化学式: C₁₇H₃₂N₂O₄
• 分子量: 328.452
• InChiKey: QMUBGMPGRWPCCA-HDJSIYSDSA-N

物化性质

• 沸点：
  441.8±20.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  76.66
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-[4-[2-(tert-butoxycarbonylamino)ethylamino]cyclohexyl]acetate 在 lithium hydroxide monohydrate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 2-((1R,4R)-4-((叔丁氧羰基)(2-((叔丁氧羰基)氨基)乙基)氨基)环己基)乙酸
  参考文献：
  名称：

  Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-β-Lactamases

  摘要：

  The bicyclic boronate VNRX-5133 (taniborbactam) is a new type of beta-lactamase inhibitor in clinical development. We report that VNRX-5133 inhibits serine-beta-lactamases (SBLs) and some clinically important metallo-beta-lactamases (MBLs), including NDM-1 and VIM-1/2. VNRX-5133 activity against IMP-1 and tested B2/B3 MBLs was lower/not observed. Crystallography reveals how VNRX-5133 binds to the class D SBL OXA-10 and MBL NDM-1. The crystallographic results highlight the ability of bicyclic boronates to inhibit SBLs and MBLs via binding of a tetrahedral (sp(3)) boron species. The structures imply conserved binding of the bicyclic core with SBLs/MBLs. With NDM-1, by crystallography, we observed an unanticipated VNRX-5133 binding mode involving cyclization of its acylamino oxygen onto the boron of the bicyclic core. Different side-chain binding modes for bicyclic boronates for SBLs and MBLs imply scope for side-chain optimization. The results further support the "high-energy-intermediate" analogue approach for broad-spectrum beta-lactamase inhibitor development and highlight the ability of boron inhibitors to interchange between different hybridization states/binding modes.

  DOI：

  10.1021/acs.jmedchem.9b00911
• 作为产物：
  描述：

  N-Boc-溴乙胺 、 ethyl 2-((1r,4r)-4-aminocyclohexyl)acetate hydrochloride 在 potassium carbonate 、 苄基三乙基氯化铵 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 19.0h， 以49%的产率得到ethyl 2-[4-[2-(tert-butoxycarbonylamino)ethylamino]cyclohexyl]acetate
  参考文献：
  名称：

  Bicyclic Boronate VNRX-5133 Inhibits Metallo- and Serine-β-Lactamases

  摘要：

  The bicyclic boronate VNRX-5133 (taniborbactam) is a new type of beta-lactamase inhibitor in clinical development. We report that VNRX-5133 inhibits serine-beta-lactamases (SBLs) and some clinically important metallo-beta-lactamases (MBLs), including NDM-1 and VIM-1/2. VNRX-5133 activity against IMP-1 and tested B2/B3 MBLs was lower/not observed. Crystallography reveals how VNRX-5133 binds to the class D SBL OXA-10 and MBL NDM-1. The crystallographic results highlight the ability of bicyclic boronates to inhibit SBLs and MBLs via binding of a tetrahedral (sp(3)) boron species. The structures imply conserved binding of the bicyclic core with SBLs/MBLs. With NDM-1, by crystallography, we observed an unanticipated VNRX-5133 binding mode involving cyclization of its acylamino oxygen onto the boron of the bicyclic core. Different side-chain binding modes for bicyclic boronates for SBLs and MBLs imply scope for side-chain optimization. The results further support the "high-energy-intermediate" analogue approach for broad-spectrum beta-lactamase inhibitor development and highlight the ability of boron inhibitors to interchange between different hybridization states/binding modes.

  DOI：

  10.1021/acs.jmedchem.9b00911