A. Mai et al., METHYL-2-THIENYLKETOPOLYMETHYLENEOXYPHENYL DERIVATIVES OF ALKYL-SUBSTITUTED 4,5-DIHYDRO-OXAZOLES WITH ANTI-HUMAN PICORNAVIRUS ACTIVITY, Antiviral chemistry & chemotherapy, 7(4), 1996, pp. 213-220
The synthesis of 5-methyl-2-thienylketopolymethylene oxyphenyl 4,5-dih
ydro-2-(alkyl)oxazoles was accomplished by the assembly of two synthon
es, namely 1-(5-methyl-2-thienyl)-7-hydroxy-1-heptanone (or 1-(5-methy
l-2-thienyl)-5-chloro-1-pentanone) and 4-[4,5-dihydro(alkyl)oxazol-2-y
l]phenol, in the presence of diethyl azodicarboxylate(DEAD)-triphenyl
phosphine (or sodium iodide and anhydrous potassium carbonate). Eighte
en new disoxaril analogues were synthesized by the above procedure and
tested in vitro against several rhino and enteroviruses. With a few e
xceptions, all test derivatives were more potent than WIN 51711 when a
ssayed against HRV-14, and as potent as WIN 51711 against HRV-2, but n
one of them inhibited the other HRV serotypes. Among the various deriv
atives, two compounds showed the same wide spectrum activity of WIN 51
711 against several rhino and enteroviruses, but were at least 10-fold
less toxic.