Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4)

We disclosed our lead optimization studies including the synthesis, molecular modeling studies and biological evaluation of a series of novel HAP inhibitors of HBV capsid assembly. This led to the identification of a novel candidate GLS4 (8n) which is now in clinical phase 2. This compound demonstrated high potency against wild and major drug-resistant HBV viral strains with IC50 values at nano molar level, pharmacokinetic and toxicology profiles of GLS4 were also reported in this article.