Synthesis and evaluation of halogenated 12N-sulfonyl matrinic butanes as potential anti-coxsackievirus agents

Eur J Med Chem. 2017 Jan 27:126:133-142. doi: 10.1016/j.ejmech.2016.09.097.

Xin-Yue Cheng ¹, Yu-Huan Li ¹, Sheng Tang ¹, Xin Zhang ¹, Yan-Xiang Wang ¹, Sheng-Gang Wang ¹, Jian-Dong Jiang ¹, Ying-Hong Li ², Dan-Qing Song ³

Affiliations

1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].

PMID: 27750147 DOI: 10.1016/j.ejmech.2016.09.097

Abstract

Twenty-eight new 12N-benzenesulfonyl matrinic butane and halogenated 12N-sulfonyl matrinic butane/ethane derivatives were designed, synthesized and evaluated for their anti-coxsakievirus activities against CVB3 taking compound 1 as the lead. SAR analysis indicated the introduction of a fluoro atom on the 1'-position might be helpful for keeping potency. Among them, compound 8a exhibited potential activities against all CVBs with IC₅₀ ranging from 0.69 to 5.14 μM, suggesting a broad-spectrum anti-coxsackievirus B feature. In addition, it also displayed an excellent PK and a good safety profile, indicating a highly druggable nature. Thus, we consider compound 8a to be a promising drug candidate in the treatment of not only viral myocarditis caused by CVB3 but also various diseases infected with coxsackieviruses B.

Keywords

Coxsakievirus; Druggability; Halogenated matrinic butane; Matrinic butane; structure−activity relationship.

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