METHYL-2-THIENYLKETOPOLYMETHYLENEOXYPHENYL DERIVATIVES OF ALKYL-SUBSTITUTED 4,5-DIHYDRO-OXAZOLES WITH ANTI-HUMAN PICORNAVIRUS ACTIVITY

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.