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  3. Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus

Synthesis and structure-activity relationship study of new biaryl amide derivatives and their inhibitory effects against hepatitis C virus

  • Eur J Med Chem. 2022 Jan 15;228:114033. doi: 10.1016/j.ejmech.2021.114033.
Yonghua Liu 1,  Jianrui Li 2,  Yuxi Gu 2,  Ling Ma 2,  Shan Cen 3,  Zonggen Peng 4,  Laixing Hu 5
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: lyh75112@163.com.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China.
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: shancen@hotmail.com.
  • 4 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: pumcpzg@126.com.
  • 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: hulaixing@hotmail.com.
PMID: 34883293 DOI: 10.1016/j.ejmech.2021.114033
Abstract

A series of novel biaryl amide derivatives were synthesized and evaluated for anti-HCV virus activity. Some significant SARs were uncovered. The intensive structural modifications led to fifteen novel compounds with more potent inhibitory activity compared to the hit compounds IMB 26 and IMB1f. Among them, compound 80 was the most active, with EC50 values almost equivalent to the clinical drug telaprevir (EC50 = 15 nM). Furthermore, it also had a good safety and in vitro and oral pharmacokinetic (oral bioavailability in rats: 34%) profile, suggesting a highly drug-like nature. Compound 80represents a more promising scaffold for anti-HCV virus activity for further study.

Keywords

Biaryl amide; HCV; Nitro group; Pharmacokinetics; Structure-activity relationship; hA3G.

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