Synthesis and evaluation of isothiazolo[4,5-b]pyridines as cyclin G-associated kinase (GAK) inhibitors

被引：1
|
作者：
Ivanova, Yulia [1 ]
Spittaels, Sander [1 ]
Gao, Ling-Jie [2 ]
Schols, Dominique [3 ]
Van Meervelt, Luc [4 ]
Froeyen, Mathy [2 ]
Dehaen, Wim [1 ]
De Jonghe, Steven [3 ]
机构：
[1] Katholieke Univ Leuven, Dept Chem, Sustainable Chem Met & Mol, Celestijnenlaan 200F, B-3001 Leuven, Belgium
[2] Katholieke Univ Leuven, Rega Inst Med Res, Dept Pharmaceut & Pharmacol Sci, Lab Med Chem, Herestr 49,box 1030, B-3000 Leuven, Belgium
[3] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol Immunol & Transplantat, Lab Virol & Chemotherapy, Herestr 49,box 1043, B-3000 Leuven, Belgium
[4] Katholieke Univ Leuven, Dept Chem, Biomol Architecture, Celestijnenlaan 200F, B-3001 Leuven, Belgium
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2024年 / 22卷 / 36期
关键词：
CLATHRIN; INSIGHTS;
D O I：
10.1039/d4ob00908h
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Isothiazolo[4,3-b]pyridines have been extensively explored as inhibitors of cyclin G-associated kinase (GAK). In order to expand the structure-activity relationship study and to discover other chemotypes that act as GAK inhibitors, the closely related isothiazolo[4,5-b]pyridine scaffold was explored. An easy and efficient synthetic procedure to access 3,5- and 3,6-dihalogenated isothiazolo[4,5-b]pyridines as key building blocks was developed. Regioselective functionalization with various substituents was performed. None of the newly synthesized isothiazolo[4,5-b]pyridines were active as GAK inhibitors. Molecular modeling was applied to rationalise their inactivity as GAK binders.
引用
收藏
页码：7373 / 7389
页数：17
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