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

页码：7373 / 7389

页数：17