ethyl 5-ethyl-3-oxoheptanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 5-ethyl-3-oxoheptanoate
• 化学式: C₁₁H₂₀O₃
• 分子量: 200.278
• InChiKey: ALBZTVMQTJCHFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-ethyl-3-oxoheptanoate 在 N,N-二异丙基乙胺 、 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 2-amino-6-(3-chlorobenzyl)-5-(2-ethylbutyl)[1,2,4]triazolo[1,5-a]pyrimidin-7(4H)-one
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5

  摘要：

  CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the highly conserved intracellular binding site in chemokine receptors provides a new avenue for the design of multitarget ligands. In this study, we synthesized and evaluated the biological activity of a series of triazolopyrimidinone derivatives in CCR2 and CCR5. Radioligand binding assays first showed that they bind to the intracellular site of CCR2, and in combination with functional assays on CCR5, we explored structure-affinity/activity relationships in both receptors. Although most compounds were CCR2-selective, 39 and 43 inhibited beta-arrestin recruitment in CCR5 with high potency. Moreover, these compounds displayed an insurmountable mechanism of inhibition in both receptors, which holds promise for improved efficacy in inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.9b00742
• 作为产物：
  描述：

  3-溴戊烷 、 乙酰乙酸乙酯 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 14.0h， 以18%的产率得到ethyl 5-ethyl-3-oxoheptanoate
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5

  摘要：

  CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the highly conserved intracellular binding site in chemokine receptors provides a new avenue for the design of multitarget ligands. In this study, we synthesized and evaluated the biological activity of a series of triazolopyrimidinone derivatives in CCR2 and CCR5. Radioligand binding assays first showed that they bind to the intracellular site of CCR2, and in combination with functional assays on CCR5, we explored structure-affinity/activity relationships in both receptors. Although most compounds were CCR2-selective, 39 and 43 inhibited beta-arrestin recruitment in CCR5 with high potency. Moreover, these compounds displayed an insurmountable mechanism of inhibition in both receptors, which holds promise for improved efficacy in inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.9b00742

文献信息

• NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Palani Anandan

  公开号：US20080019978A1

  公开（公告）日：2008-01-24

  The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, esters, and tautomers thereof, wherein: Q is selected from the group consisting of: and L is selected from the group consisting of: pharmaceutically compositions comprising one or more compounds of formula (I), and methods of using the compounds of formula (I).

  本发明提供了式（I）的化合物及其药学上可接受的盐，溶剂化合物，酯和互变异构体，其中： Q选自以下组： L选自以下组： 本发明还提供了包含一种或多种式（I）化合物的药学组合物以及使用式（I）化合物的方法。
• Nitrogen-containing heterocyclic compounds and methods of use thereof
  申请人：Palani Anandan

  公开号：US20070066630A1

  公开（公告）日：2007-03-22

  The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, esters, and tautomers thereof, wherein: Q is selected from the group consisting of: L is selected from the group consisting of: pharmaceutically compositions comprising one or more compounds of formula (I), and methods of using the compounds of formula (I).

  本发明提供了式（I）化合物及其药学上可接受的盐、溶剂化合物、酯和互变异构体，其中：Q选自以下组：L选自以下组：包括一种或多种式（I）化合物的药学组合物，以及使用式（I）化合物的方法。
• ORTHO-CONDENSED 2-PYRIDINONE DERIVATIVES AS NICOTINIC ACID RECEPTOR AGONISTS FOR THE TREATMENT OF DYSLIPIDEMIA
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1885726B1

  公开（公告）日：2016-12-14
• US7723342B2
  申请人：——

  公开号：US7723342B2

  公开（公告）日：2010-05-25
• US7737155B2
  申请人：——

  公开号：US7737155B2

  公开（公告）日：2010-06-15