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

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

  • Bioorg Med Chem. 2020 Jan 1;28(1):115188. doi: 10.1016/j.bmc.2019.115188.
Belén Martinez-Gualda 1,  Szu-Yuan Pu 2,  Mathy Froeyen 1,  Piet Herdewijn 1,  Shirit Einav 2,  Steven De Jonghe 3
Affiliations

Affiliations

  • 1 KU Leuven, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Herestraat 49, 3000 Leuven, Belgium.
  • 2 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3 KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000 Leuven, Belgium. Electronic address: steven.dejonghe@kuleuven.be.
PMID: 31757682 DOI: 10.1016/j.bmc.2019.115188
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.

Keywords

Antiviral drugs; Cyclin G-associated kinase; Dengue virus; Isothiazolo[4,3-b]pyridine; Kinase inhibitor.

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