title: QSAR analysis of [(biphenyloxy)propyl]isoxazoles: agents against coxsackievirus B3.
abstract: BACKGROUND
  Antiviral drugs are urgently needed for the treatment of acute and chronic diseases caused by enteroviruses such as coxsackievirus B3 (CVB3). The main goal of this study is quantitative structure-activity relationship (QSAR) analysis of anti-CVB3 activity (clinical CVB3 isolate 97927 [log IC50, µM]) and investigation of the selectivity of 25 ([biphenyloxy]propyl)isoxazoles, followed by computer-aided design and virtual screening of novel active compounds.
  
  
  CONCLUSIONS
  The 2D QSAR obtained models are quite satisfactory (R(2) = 0.84-0.99, Q(2) = 0.76-0.92, R(2)(ext) = 0.62-0.79). Compounds with high antiviral activity and selectivity have to contain 5-trifluoromethyl-[1,2,4]oxadiazole or 2,4-difluorophenyl fragments. Insertion of 2,5-dimethylbenzene, napthyl and especially biphenyl substituents into investigated compounds substantially decreases both their antiviral activity and selectivity. Several compounds were proposed as a result of design and virtual screening. A high level of activity of 2-methoxy-1-phenyl-1H-imidazo[4,5-c]pyridine (sm428) was confirmed experimentally.
  
  
  CONCLUSIONS
  Simplex representation of molecular structure allows successful QSAR analysis of anti-CVB3 activity of ([biphenyloxy]propyl)isoxazole derivatives. Two possible ways of battling CVB3 are considered as a future perspective.
authors.affiliation: Department of Molecular Structure, AV Bogatsky Physical Chemical Institute, National Academy of Sciences of Ukraine, Odessa, Ukraine. murik@email.unc.edu
authors.forename: Eugene N
authors.initials: EN
authors.lastname: Muratov
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Varlamova
authors.forename: Anatoly G
authors.initials: AG
authors.lastname: Artemenko
authors.forename: Tat'yana
authors.initials: T
authors.lastname: Khristova
authors.forename: Victor E
authors.initials: VE
authors.lastname: Kuz'min
authors.forename: Vadim A
authors.initials: VA
authors.lastname: Makarov
authors.forename: Olga B
authors.initials: OB
authors.lastname: Riabova
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmidtke
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D003384:Coxsackievirus Infections / Q000188:drug therapy*; D015195:Drug Design; D029822:Enterovirus B, Human / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007555:Isoxazoles