Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents
| Autor: | Sheng Tang, Dan-Qing Song, Xin Zhang, Xin-Yue Cheng, Jian-Dong Jiang, Zong-Gen Peng, Wen-Jing Li, Ying-Hong Li |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Anti hiv Stereochemistry Compound 17 Substituent General Chemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry In vivo 030220 oncology & carcinogenesis Amide Structure–activity relationship Potency Biological evaluation |
| Zdroj: | Chinese Chemical Letters. 27:1052-1057 |
| ISSN: | 1001-8417 |
| DOI: | 10.1016/j.cclet.2016.03.006 |
| Popis: | 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 of matrinic amide might greatly enhance the potency. Among them, matrinic acid 17 and N ′-substituted matrinic amides 18a – d exhibited promising potency with low micromolar EC 50 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. |
| Databáze: | OpenAIRE |
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