N-Substituted Matrinic Acid Derivatives:Anti-Heptitis C Virus Agents through down-regulating Host Heat-Stress Cognate Protein 70(Hsc70) Expression

作     者：Na-Na Du~+,Zong-Gen Peng~+,Yan-Xin Liu,Jian-Rui Li,Li-Mei Gao,Chong-Wen Bi,Yan-Xing Han,Yan-Xiang Wang,Zhou-Yi Wu,Jian-Dong Jiang,~* Dan-Qing Song~* Institute of Medicinal Biotechnology,Chinese Academy of Medical Science and Peking Union Medical College,NO.2 Nanwei Road,Xuanwu District,Beijing 100050,China. 

会议名称：《2011年全国药物化学学术会议——药物的源头创新》

会议日期：2011年

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

关 键 词：Hsc70 anti-HCV N-substituted matrinic acid 

摘      要：Host heat shock cognate protein 70(Hsc70) plays an important role in HCV replication, and it has been demonstrated to be a novel target against HCV.N-p-methoxybenzyl matrinic acid(1) was found to be an effective Hsc70 down-regulator with good *** using 1 as the lead, twenty-two analogues were synthesized and evaluated for their anti-HCV activity in *** SAR analysis revealed that 1)the benzyl group at the 12-N atom was necessary for activity;2) introduction of electron-drawing substituents might significantly enhance the *** compounds were studied for their safe and pharmacokinetic studies in vivo,among which compounds 8c and 8m exhibited greater anti-HCV activity(SI23) than that of *** addition,both of them showed good safety(LD1000 mg/kg) and oral *** consider 8c and 8m to be promising anti-HCV drug candidates for further investigation.