title: SAR evolution and discovery of benzenesulfonyl matrinanes as a novel class of potential coxsakievirus inhibitors.
abstract: Fifty-one novel 12N-substituted matrinic acid derivatives were synthesized and evaluated for their anti-coxsackievirus B3 activities.
  
  
  
  Structure-activity relationship studies revealed that the 11-side chain could be determinant for the selectivity index by adjusting overall lipophilicity, and 11-butane was the best one for both potency and druggability. The optimized 35d showed the broad-spectrum anti-coxsackieviruse effects, an excellent pharmacokinetics and a good safety profile. More importantly, it displayed a potential effect for the pleconaril-resistant coxsackievirus B3 as well. Its mode of action is targeting on the viral transcription and translation stage, a different mechanism from that of pleconaril.
  
  
  
  Thus, we considered that 35d is a promising anti-enteroviral candidate for the treatment of various diseases infected with coxsackieviruses.
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Sheng
authors: S
authors: Tang
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Yu-Huan
authors: YH
authors: Li
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Xin-Yue
authors: XY
authors: Cheng
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Ying-Hong
authors: YH
authors: Li
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Hui-Qiang
authors: HQ
authors: Wang
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Lan-Ying
authors: LY
authors: Kong
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Xin
authors: X
authors: Zhang
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.|State Key Laboratory of Bioactive Substance & Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors: Jian-Dong
authors: JD
authors: Jiang
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors: Dan-Qing
authors: DQ
authors: Song
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000821:virology; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D004770:Enterovirus / Q000187:drug effects*; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology; D010080:Oxazoles; D012367:RNA, Viral / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D000998:Antiviral Agents; D007546:Isoquinolines; D010069:Oxadiazoles; D010080:Oxazoles; D012367:RNA, Viral; D013449:Sulfonamides; D014764:Viral Proteins; C115201:pleconaril; D012697:Serine Endopeptidases; C485595:matriptase
keywords: coxsackieviruse; druggability; matrinane; matrinic acid; structure–activity relationship