title: Synthesis and evaluation of halogenated 12N-sulfonyl matrinic butanes as potential anti-coxsackievirus agents.
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 IC50ranging 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.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Cheng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Yan-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Sheng-Gang
authors.initials: SG
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: yinghongli523@aliyun.com.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: songdanqingsdq@hotmail.com.
authors.forename: Dan-Qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002073:Butanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D060326:Chemistry Techniques, Synthetic; D002522:Chlorocebus aethiops; D015195:Drug Design; D029822:Enterovirus B, Human / Q000187:drug effects*; D054879:Halogenation; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D002073:Butanes
keywords: Coxsakievirus; Druggability; Halogenated matrinic butane; Matrinic butane; structure−activity relationship