PYRROLO[2,3-B]PYRAZINE COMPOUNDS AS CCCDNA INHIBITORS FOR THE TREATMENT OF HEPATITIS B VIRUS (HBV) INFECTION

The present invention relates to novel therapeutic agents against hepatitis B virus (HBV) infection, particularly inhibitors of viral covalently closed circular DNA (cccDNA) which is the key barrier for HBV cure. Accordingly, the invention provides the pyrrolo[2,3-b]pyrazine compounds of formula (I), as described and defined herein, for use in the treatment of HBV infection. The compounds providedherein are highly potent against HBV infection and enable an improved therapy, particularly of chronic HBV infection and HBV rebound. The present invention further relates to a novel screening assayfor the identification of therapeutic agents against HBV infection, particularly cccDNA inhibitors, which is performed in hepatocyte-like cells that recapitulate the complete HBV life cycle followinginfection with patient-derived HBV. 本发明涉及针对乙型肝炎病毒(HBV)感染的新治疗剂，特别是用于HBV治愈的关键障碍的病毒共价闭合环状DNA(cccDNA)的抑制剂。因此，本发明提供了如本文所述和定义的式(I)的吡咯并[2,3-b]吡嗪化合物，其用于治疗HBV感染。本文提供的化合物对HBV感染高度有效，并且能够改善治疗，特别是对于慢性HBV感染和HBV反弹。本发明还涉及用于鉴定抗HBV感染的治疗剂、特别是cccD