4-{[3-(methyloxy)phenyl]amino}-3-quinolinecarboxamide | 1191913-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-{[3-(methyloxy)phenyl]amino}-3-quinolinecarboxamide
• 英文别名: 4-[(3-methoxyphenyl)amino]quinoline-3-carboxamide；4-(3-Methoxyanilino)quinoline-3-carboxamide
• CAS: 1191913-41-3
• 化学式: C₁₇H₁₅N₃O₂
• 分子量: 293.325
• InChiKey: XCDXNBRLAKWTDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-Chloro-1,4-dihydroquinoline-3-carboxamide 、 间氨基苯甲醚 以 乙腈 为溶剂， 生成 4-{[3-(methyloxy)phenyl]amino}-3-quinolinecarboxamide
  参考文献：
  名称：

  Quinolines as a novel structural class of potent and selective PDE4 inhibitors. Optimisation for inhaled administration

  摘要：

  Crystallography driven optimisation of a lead derived from similarity searching of the GSK compound collection resulted in the discovery of quinoline-3-carboxamides as highly potent and selective inhibitors of phosphodiesterase 4B. This series has been optimized to GSK256066, a potent PDE4B inhibitor which also inhibits LPS induced production of TNF-alpha from isolated human peripheral blood mononuclear cells with a pIC(50) of 11.1. GSK256066 also has a suitable pro. le for inhaled dosing. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.012

文献信息

• New quinoline-based PDE4 inhibitors through GSK-256066 fragment-based elaboration
  作者：Letizia Crocetti、Maria Paola Giovannoni、Claudia Vergelli、Gabriella Guerrini、Fabrizio Melani、Agostino Cilibrizzi

  DOI：10.1016/j.molstruc.2023.136719

  日期：2024.1

  fragment-based drug design methodologies on a fragment of GSK-256066 - i.e. a previously discovered lead compound, which was developed by GlaxoSmithKline. This approach led to the identification of several new and potent PDE4 inhibitors with IC50 values in the low nanomolar range (e.g. 5e with IC50 = 21.27 nM, 7e with IC50 = 33.47 nM and 5p with IC50 = 44.57 nM). In addition to the analysis of SARs, herein

  我们在这里报告了一系列新的喹啉作为 PDE4 抑制剂，是通过基于片段的药物设计方法对 GSK-256066 的片段（即先前发现的先导化合物，由葛兰素史克开发）获得的。这种方法导致了几种新的有效 PDE4 抑制剂的鉴定，其 IC 50值在低纳摩尔范围内（例如5e的 IC 50  = 21.27 nM、7e的 IC 50  = 33.47 nM 和5p的 IC 50 = 44.57 nM）。除了 SAR 分析之外，本文还报告了对接和分子动力学研究，以进一步评估在喹啉支架的选定位置引入的各种取代基如何影响分子的生物活性。