Synthesis, structure–activity relationships, and SARS-CoV-2 antiviral activity of 3,5-disubstituted isothiazolo[4,3-b]pyridines as PIKfyve inhibitors
Ling‐Jie Gao·Steven De Jonghe·Chieh Wen Lo·Aakriti Gangwal·Do Hoang Nhu Tran·Jef Rozenski·Dominique Schols·Mathy Froeyen·Wim Dehaen·Shirit Einav·Demian Kalebić
Introduction 3-Alkynyl-6-aryl-isothiazolo[4,3-b]pyridines have previously been shown to be potent inhibitors of the lipid kinase FYVE finger-containing phosphoinositide kinase (PIKfyve), displaying broad-spectrum antiviral activity. Methods To further study their structure–activity relationship (SAR), an efficient synthesis toward 3- bromo-5-chloro-isothiazolo[4,3-b]pyridine was established. It allowed to introduce structural modifications at positions 3 and 5 by palladium-catalyzed cross-coupli