Citation: Sheng Tang, Zong-Gen Peng, Xin Zhang, Xin-Yue Cheng, Wen-Jing Li, Jian-Dong Jiang, Ying-Hong Li, Dan-Qing Song. Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents[J]. Chinese Chemical Letters, ;2016, 27(7): 1052-1057. doi: 10.1016/j.cclet.2016.03.006 shu

Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents

Beijing Key Laboratory of Anti-infective Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China

Author Bio:

E-mail address: songdanqingsdq@hotmail.com (D.-Q. Song)
Received Date: 30 November 2015
Revised Date: 4 February 2016
Accepted Date: 4 March 2016
Available Online: 15 July 2016

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A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine (1) and evaluated for their anti-HCV activity, taking compound 2 as the lead. SAR revealed that the introduction of a suitable substituent at the N'-end ofmatrinic amide might greatly enhance the potency. Among them, matrinic acid 17 and N'-substituted matrinic amides 18a-d exhibited promising potency with low micromolar EC₅₀ values ranging from 1.03 μmol/L to 7.54 μmol/L, and better therapeutic window with SI from 66 to 132. Moreover, compound 17 displayed an excellent PK and safety profile in vivo, demonstrating good drug-like characteristics. Thus, it has been selected for further investigation, with an advantage of decreased chances of inducing drug-resistance mutations.
- Matrinic acid,
- Matrinic amide,
- Hepatitis C virus,
- Structure-activity relationship
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