1-Ethyl-6-fluoro-7-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid | 168031-11-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-Ethyl-6-fluoro-7-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 168031-11-6
• 化学式: C₂₀H₂₅FN₄O₅
• 分子量: 420.441
• InChiKey: WEEPOTWDRYRDGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluoroaniline 、 1-Ethyl-6-fluoro-7-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 生成 N-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)-3-fluorophenyl)-1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Quinolone antibiotic derivatives as new selective Axl kinase inhibitors

  摘要：

  Axl is a new promising molecular target for antineoplastic therapies. A series of quinolone antibiotic derivatives were designed and synthesized as new selective Axl inhibitors. One of the most promising compound 8i bound tightly to Axl with a K-d value of 1.1 nM, and inhibited its kinase activity with an IC50 value of 26 nM. The compound also significantly inhibited the phosphorylation of Axl and dose dependently inhibited cell invasion and migration in TGF-beta 1 induced MDA-MD-231 breast cancer cells. In addition, 8i demonstrated reasonable pharmacokinetic properties and exhibited extraordinary target selectivity over 468 kinases except for Flt3 (IC50 = 50 nM)), with a S(10) and S(35) value of 0.022 and 0.42 at 1.0 mu M, respectively. Compound 8i may serve as a new valuable lead compound for future anti-cancer drug discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.065
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 依诺沙星 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-Ethyl-6-fluoro-7-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Quinolone antibiotic derivatives as new selective Axl kinase inhibitors

  摘要：

  Axl is a new promising molecular target for antineoplastic therapies. A series of quinolone antibiotic derivatives were designed and synthesized as new selective Axl inhibitors. One of the most promising compound 8i bound tightly to Axl with a K-d value of 1.1 nM, and inhibited its kinase activity with an IC50 value of 26 nM. The compound also significantly inhibited the phosphorylation of Axl and dose dependently inhibited cell invasion and migration in TGF-beta 1 induced MDA-MD-231 breast cancer cells. In addition, 8i demonstrated reasonable pharmacokinetic properties and exhibited extraordinary target selectivity over 468 kinases except for Flt3 (IC50 = 50 nM)), with a S(10) and S(35) value of 0.022 and 0.42 at 1.0 mu M, respectively. Compound 8i may serve as a new valuable lead compound for future anti-cancer drug discovery. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.01.065

文献信息

• [EN] COMPOUNDS AND METHODS FOR MODULATING THE SILENCING OF A POLYNUCLEOTIDE OF INTEREST<br/>[FR] COMPOSÉS ET PROCÉDÉS DE MODULATION DE SILENÇAGE D'UN POLYNUCLÉOTIDE D'INTÉRÊT
  申请人：UNIV EMORY

  公开号：WO2008073957A2

  公开（公告）日：2008-06-19

  (EN) Methods and compositions comprising chemical compounds that modulate the silencing of a polynucleotide of interest in a cell are provided. Such chemical compounds when used in combination with an appropriate silencing element can be used to modulate (e.g., increase) the level of the polynucleotide targeted by the silencing element. Methods of using such compositions both in therapies involving RNAi -mediated suppression of gene expression, as well as, in vitro methods that allow for the targeted modulation of expression of a polynucleotide of interest are provided. Pharmaceutical or cosmetic compositions comprising such compounds and silencing elements also are disclosed. Methods for screening a compound of interest for the ability to modulate the activity of a heterologous silencing element also are provided.(FR) L'invention concerne des procédés et des compositions comprenant des composés chimiques pour moduler le silençage d'un polynucléotide d'intérêt dans une cellule. En combinaison avec un élément de silençage approprié, de tels composés chimiques peuvent être utilisés pour moduler (par exemple, augmenter) le taux du polynucléotide ciblé par l'élément de mise au silence. Sont décrits les procédés d'utilisation de telles compositions à la fois dans les thérapies impliquant la suppression de l'expression génique induite par l'ARNi et dans les procédés in vitro qui permettent la modulation ciblée de l'expression d'un polynucléotide d'intérêt. Des compositions pharmaceutiques ou cosmétiques renfermant de tels composés et éléments de silençage sont également décrites. Sont enfin décrits les procédés de criblage d'un composé d'intérêt en vue de déterminer sa capacité à moduler l'activité d'un élément de silençage hétérologue.