Arylketotetramethylene analogues of disoxaril (WIN 51711) were synthesized by reaction of 1-aryl-5-chloropentan-1-ones with 2-(4-hydroxyphenyl)-4,5-dihydro oxazoles, ethyl 4-hydroxybenzoates and 4-hydroxybenzonitrile. The new derivatives were tested for antiviral activity against various human rhinovirus (HRV) serotypes. The best activity was exhibited by the ethoxycarbonyl derivatives, whereas the oxazoline counterparts were less active and the cyano derivatives totally inactive. 5-[4-(4,5-Dihydro-2-oxazolyl)phenoxy]-1-(4-methoxyphenyl)pentan-1-one and ethyl 4-[5-(4-methylthiophenyl)-5-oxopentoxy] benzoate were more active than, and as active as, disoxaril, respectively, against HRV-14. Moreover, they were 10 times less cytotoxic.
AndriesKDewindtBSnoeksJWillebrordsRStokbroekxR & LewiPJ (1991) A comparative test of fifteen compounds against all known human rhinovirus serotypes as a basis for a more rational screening program. Antiviral Research16:213–225.
2.
ArticoMBottaMCorelliFMaiAMassaS & RagnoR (1996) Investigation on QSAR and binding mode of a new class of human rhinovirus-14 inhibitors by CoMFA and docking experiments. Bioorganic and Medicinal Chemistry4:1715–1724.
3.
AshRJParkerRAHaganAC & MayerGD (1979) RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]ethanone), a new antirhinovirus compound. Antimicrobial Agents and Chemotherapy16:301–305.
4.
BaileyTRDianaGDKowalczykPJAkullianVEissenstatMACutcliffeDMallamoJPCarabateasPM & PevearDC (1992) Antirhinoviral activity of heterocyclic analogs of WIN 54954. Journal of Medicinal Chemistry35:4628–4633.
5.
BaileyTRDianaGDMallamoJPVescioNDraperTLCarabateasPMLongMAGirandaVLDutkoFJ & PevearDC (1994) An evaluation of the antirhinoviral activity of acylfuran replacements for 3-methylisoxazoles. Are 2-acetylfurans bioisosteres for 3-methylisoxazoles?Journal of Medicinal Chemistry37:4177–4184.
6.
CaligurryLAMcSharryJJ & LawrenceGW (1980) Effect of arildone on modifications of poliovirus in vitro. Virology105:86–93.
7.
DianaGDMcKinlayMAOttoMJAkullianV & OglesbyC (1985) [[(4,5-Dihydro-2-oxazolyl)phenoxy]alkyl]isoxazoles. Inhibitors of picornavirus uncoating. Journal of Medicinal Chemistry28:1906–1910.
8.
DianaGDCutcliffeDOglesbyRCOttoMJMallamoJPAkullianV & McKinlayMA (1989) Synthesis and structure–activity studies of some disubstituted phenylisoxazoles against human picornavirus. Journal of Medicinal Chemistry32:450–455.
MaiAArticoMMassaSRagnoRDe MontisACorriasSSpigaMG & La CollaP (1996) Methyl-2-thienylketopolymethyylene oxyphenyl derivatives of alkyl-substituted 4,5-dihydro-oxazoles with anti-human picornavirus activity. Antiviral Chemistry and Chemotherapy7:213–220.
11.
MassaSArticoMMaiARagnoRCorelliFPaniAMarongiuMETramontanoE & La CollaP (1991) Synthesis of new disoxaril analogues with potent and selective anti-human rhinovirus 14 activity. Bioorganic and Medicinal Chemistry Letters1:575–578.
12.
MassaSCorelliFArticoMMaiARagnoRDe MontisALoiAGCorriasSMarongiuME & La CollaP (1995) [[[(Thienylcarbonyl)alkyl]oxy]phenyl]- and [[[(pyrrylcarbonyl)-alkyl]oxy]phenyl]oxazoline derivatives with potent and selective anti-human rhinovirus activity. Journal of Medicinal Chemistry38:803–809.
13.
NinomiyaYOhsawaCAyoamaMUmedaISuharaY & IshitsukaH (1984) Antivirus agent, Ro 09–0410, binds to rhinovirus specifically and stabilizes the virus conformation. Virology134:269–276.
14.
OttoMJFoxMPFancherMJKuhrtMFDianaGD & McKinleyMA (1985) In vitro activity of WIN 51711, a new broad spectrum antipicornavirus drug. Antimicrobial Agents and Chemotherapy27:883–886.
15.
PastoDJ & ServeMP (1965) Neighbouring group participation by carbonyl oxygen. Journal of the American Chemical Society87:1515–1521.
16.
Solov'evVMKurochkinaN & SkoldinovAP (1967) α,ω-Substituted alkenes with possible biological significance. VII. Synthesis of p-fluoro phenyl(ω-aminoalkyl)ketones. Zhurnal Obshchei Khimica37:1233–1236.
