Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Cyclin G-associated kinase, Isothiazolo[4,3-b]pyridine, Dengue virus, Kinase inhibitor, Antiviral drugs, CLATHRIN COAT, DENGUE VIRUS, INHIBITORS, IDENTIFICATION, OPTIMIZATION, BINDING, Antiviral Agents, Cell Line, Dengue Virus, Dose-Response Relationship, Drug, Humans, Intracellular Signaling Peptides and Proteins, Microbial Sensitivity Tests, Molecular Structure, Protein Kinase Inhibitors, Protein Serine-Threonine Kinases, Pyridines, Structure-Activity Relationship, Thiazoles, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

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.