Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors

被引：27

作者：

Elagawany, Mohamed ^{[1
,2
,3
]}

Ibrahim, Mohamed A. ^{[1
,2
,4
]}

Ahmed, Hany Emary Ali ^{[3
,5
]}

El-Etrawy, A. Sh ^{[2
]}

Ghiaty, Adel ^{[3
]}

Abdel-Samii, Zakaria K. ^{[4
]}

El-Feky, Said A. ^{[4
]}

Bajorath, Juergen ^{[6
]}

机构：

[1] Univ Strasbourg, Fac Pharm, UMR 7200, Lab Innovat Therapeut, F-67401 Illkirch Graffenstaden, France

[2] Misr Univ Sci & Technol, Coll Pharm, Dept Organ Chem, Al Motamayez District, Egypt

[3] Al Azhar Univ, Dept Organ Chem, Fac Pharm, Cairo 11884, Egypt

[4] Zagazig Univ, Dept Organ Pharmaceut Chem, Fac Pharm, Zagazig 44519, Egypt

[5] Taibah Univ, Coll Pharm, Pharmacognosy & Pharmaceut Chem Dept, Al Madinaha Al Munawarah, Saudi Arabia

[6] Univ Bonn, LIMES Program Unit Chem Biol & Med Chem, B IT, Dept Life Sci Informat, D-53113 Bonn, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 07期

关键词：

Pyridazinone; Phthalazinone; Kinases; Docking; GSK3; GLYCOGEN-SYNTHASE KINASE-3; CYCLIN-DEPENDENT KINASES; PHARMACOLOGICAL INHIBITORS; STRUCTURAL REQUIREMENTS; GSK-3-BETA; POTENT; SAR;

D O I：

10.1016/j.bmcl.2013.02.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2007 / 2013

页数：7

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