2. Academic Validation
  3. Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus

Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus

  • J Med Chem. 2023 Oct 6. doi: 10.1021/acs.jmedchem.3c01145.
Buyu Kou 1 2,  Zhisen Zhang 1 2,  Xingchun Han 1 2,  Zheng Zhou 2 3,  Zhiheng Xu 2 3,  Xue Zhou 1 4,  Fang Shen 1 4,  Yuan Zhou 1 4,  Xiaojun Tian 1 4,  Guang Yang 1 4,  John A T Young 5 4,  Hongxia Qiu 1 6,  Giorgio Ottaviani 1 6,  Alexander Mayweg 5 2,  Wei Zhu 1 2,  Hong C Shen 1 2,  Haixia Liu 1 2,  Taishan Hu 1 2
Affiliations

Affiliations

  • 1 China Innovation Center of Roche, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
  • 2 Medicinal Chemistry, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
  • 3 Lead Discovery, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
  • 4 Discovery Virology, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
  • 5 Roche Innovation Center Basel, Roche Pharma Research and Early Development, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
  • 6 Pharmaceutical Sciences, Building 5, 371 Lishizhen Road, Shanghai 201203, China.
PMID: 37801325 DOI: 10.1021/acs.jmedchem.3c01145
Abstract

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos(t)ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration.

Figures
Products