2. Academic Validation
  3. Synthesis and evaluation of N-sulfonylpiperidine-3-carboxamide derivatives as capsid assembly modulators inhibiting HBV in vitro and in HBV-transgenic mice

Synthesis and evaluation of N-sulfonylpiperidine-3-carboxamide derivatives as capsid assembly modulators inhibiting HBV in vitro and in HBV-transgenic mice

  • Eur J Med Chem. 2023 Mar 5;249:115141. doi: 10.1016/j.ejmech.2023.115141.
Jiaxin Yin 1,  Zhongqi Feng 1,  Zhi Li 2,  Jieli Hu 1,  Yuan Hu 1,  Xuefei Cai 1,  Hui Zhou 3,  Kai Wang 1,  Ni Tang 1,  Ailong Huang 1,  Luyi Huang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
  • 2 Department of Breast＆thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400010, China.
  • 3 Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
  • 4 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: heligent@cqmu.edu.cn.
PMID: 36709646 DOI: 10.1016/j.ejmech.2023.115141
Abstract

The hepatitis B virus (HBV) capsid assembly modulators (CAMs) have been developed as effective anti-HBV agents in the treatment of chronic HBV Infection by targeting the HBV core protein and inducing the formation of aberrant or morphologically normal capsid. However, some CAMs have been observed adverse events such as ALT flares and rash. Therefore, finding new CAMs is of great importance. In this report, we synthesized N-sulfonylpiperidine-3-carboxamides (SPCs) derivatives and evaluated their anti-HBV activities. Among the SPC derivatives, compound C-49 notably suppressed HBV replication in HepAD38, HepG2-HBV1.3 and HepG2-NTCP cells. Moreover, treatment with C-49 for 12 days exhibited potent anti-HBV activity (100 mg/kg; 2.42 log reduction of serum HBV DNA) in HBV-transgenic mice without apparent hepatotoxicity. Our findings provided a new SPC derivative as HBV capsid assembly modulator for developing safe and efficient anti-HBV therapy.

Keywords

Antiviral agent; Capsid assembly modulator; Core protein; HBV; Sulfonylpiperidine.

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