ethyl 3-(3-ethoxy-N-(2-morpholino-2-oxoethyl)-3-oxopropanamido)-5-(4-fluorobenzyl)picolinate | 1345733-99-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 3-(3-ethoxy-N-(2-morpholino-2-oxoethyl)-3-oxopropanamido)-5-(4-fluorobenzyl)picolinate
• CAS: 1345733-99-4
• 化学式: C₂₆H₃₀FN₃O₇
• 分子量: 515.539
• InChiKey: HRXTUGAHZOMQSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  37.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  115.34
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-ethoxy-N-(2-morpholino-2-oxoethyl)-3-oxopropanamido)-5-(4-fluorobenzyl)picolinate 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 7-[(4-Fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-1-[2-(4-morpholinyl)-2-oxoethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide substituent effects with C3 amide groups

  摘要：

  A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.011
• 作为产物：
  描述：

  ethyl 3-amino-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate 在 sodium cyanoborohydride 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 3-(3-ethoxy-N-(2-morpholino-2-oxoethyl)-3-oxopropanamido)-5-(4-fluorobenzyl)picolinate
  参考文献：
  名称：

  Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide substituent effects with C3 amide groups

  摘要：

  A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.011

文献信息

• Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors
  作者：Brian A. Johns、Takashi Kawasuji、Jason G. Weatherhead、Eric E. Boros、James B. Thompson、Edward P. Garvey、Scott A. Foster、Jerry L. Jeffrey、Wayne H. Miller、Noriyuki Kurose、Kenichi Matsumura、Tamio Fujiwara

  DOI：10.1016/j.bmcl.2011.08.082

  日期：2011.11

  A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity. (C) 2011 Published by Elsevier Ltd.