Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2-<i>c</i>]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment

Abstract

The discovery of novel tetrahydropyrrolo[1,2-<i>c</i>]pyrimidines derivatives from <b>Bay41_4109</b> as hepatitis B virus (HBV) inhibitors is herein reported. The structure-activity relationship optimization led to one highly efficacious compound <b>28a</b> (IC₅₀ = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of <b>28a</b> against HBV replication.