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ID: ALA4609987

Journal: Bioorg Med Chem

Title: Structure-activity relationship study of the pyridine moiety of isothiazolo[4,3-b]pyridines as antiviral agents targeting cyclin G-associated kinase.

Authors: Martinez-Gualda B, Pu SY, Froeyen M, Herdewijn P, Einav S, De Jonghe S.

Abstract: Previously, we reported the discovery of 3,6-disubstituted isothiazolo[4,3-b]pyridines as potent and selective cyclin G-associated kinase (GAK) inhibitors with promising antiviral activity. In this manuscript, the structure-activity relationship study was expanded to synthesis of isothiazolo[4,3-b]pyridines with modifications of the pyridine moiety. This effort led to the discovery of an isothiazolo[4,3-b]pyridine derivative with a 3,4-dimethoxyphenyl residue at position 5 that displayed low nanomolar GAK binding affinity and antiviral activity against dengue virus.

CiteXplore: 31757682

DOI: 10.1016/j.bmc.2019.115188