3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide
• 英文别名: 3-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-[3-[(4-methylpiperazin-1-yl)methyl]-5-(trifluoromethyl)phenyl]benzamide
• 化学式: C₂₉H₂₇F₃N₆O
• 分子量: 532.568
• InChiKey: AYQXKPMEHPZRKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氨基-4-甲基苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 硫酸 、 potassium tert-butylate 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2

  摘要：

  Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, Sn, tightly bound to DDR1 and DDR2 proteins with K-d values of 7.9 and 8.0 nM; potently inhibited the kinases with IC50 values of 9.4 and 20.4 nM, respectively; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 mu M. DDR1- and DDR2-kinase inhibition by 5n was validated by Western-blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.

  DOI：

  10.1021/acs.jmedchem.8b01045

文献信息

• Bicyclic heteroaryl compounds
  申请人：Zou Dong

  公开号：US20070191376A1

  公开（公告）日：2007-08-16

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及通式如下的化合物：其中变量基团如本文所定义，以及它们的制备和使用。
• Bicyclic Heteroaryl Compounds
  申请人：Zou Dong

  公开号：US20120135986A1

  公开（公告）日：2012-05-31

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及一般公式中的化合物：其中变量基团如本文所定义，并涉及它们的制备和使用。
• Methods and Compositions for Treating Parkinson's Disease
  申请人：Shakespeare William C.

  公开号：US20140066434A1

  公开（公告）日：2014-03-06

  The invention discloses methods and compositions for treating or preventing Parkinson's disease by administering a compound of Formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

  本发明揭示了使用式(I)化合物或其药学上可接受的盐、溶剂或水合物治疗或预防帕金森病的方法和组合物，其中变量的定义如本文所述。
• SUBSTITUTED ACETYLENIC PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS KINASE INHIBITORS
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US20190031656A1

  公开（公告）日：2019-01-31

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.
• US8114874B2
  申请人：——

  公开号：US8114874B2

  公开（公告）日：2012-02-14