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

作者全名："Yin, Jiaxin; Feng, Zhongqi; Li, Zhi; Hu, Jieli; Hu, Yuan; Cai, Xuefei; Zhou, Hui; Wang, Kai; Tang, Ni; Huang, Ailong; Huang, Luyi"

作者地址："[Yin, Jiaxin; Feng, Zhongqi; Hu, Jieli; Hu, Yuan; Cai, Xuefei; Wang, Kai; Tang, Ni; Huang, Ailong; Huang, Luyi] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Key Lab Mol Biol Infect Dis,Minist Educ,Dept Infec, Chongqing 400010, Peoples R China; [Li, Zhi] Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & thyroid Surg, Chongqing 400010, Peoples R China; [Zhou, Hui] Chongqing Med Univ, Coll Pharm, Chongqing Res Ctr Pharmaceut Engn, Chongqing 400016, Peoples R China"

通信作者："Huang, LY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Key Lab Mol Biol Infect Dis,Minist Educ,Dept Infec, Chongqing 400010, Peoples R China."

来源：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ESI学科分类：CHEMISTRY

WOS号：WOS:000927466300001

JCR分区：Q1

影响因子：6

年份：2023

卷号：249

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：HBV; Core protein; Sulfonylpiperidine; Capsid assembly modulator; Antiviral agent

摘要："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 forma-tion 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."

基金机构："National Natural Science Foundation of China [U20A20392, 82002615]; 111 Project [D20028]; Innovative and Entrepreneurial Team of Chongqing Talents Plan; Scientific Research Project [CSTB2022BSXM-JCX0052]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202000418, KJZD-M202000401, HZ2021006]; Chongqing Med-ical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) [2023DBXM007]; Kuanren talents program of the second affiliated hospital of Chongqing Medical University; Future Medical Youth Innovation Team of Chongqing Medical University [W0036, W0101]"

基金资助正文："Acknowledgments Support for this research was provided by the National Natural Science Foundation of China (U20A20392, 82002615) , the 111 Project (No. D20028) , the Innovative and Entrepreneurial Team of Chongqing Talents Plan, Chongqing PhD ?Through Train? Scientific Research Project (CSTB2022BSXM-JCX0052) , the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202000418, KJZD-M202000401, HZ2021006) , Chongqing Med-ical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2023DBXM007) , the Kuanren talents program of the second affiliated hospital of Chongqing Medical University, the Future Medical Youth Innovation Team of Chongqing Medical University (W0036, W0101) ."