A number of 2,6-disubstituted analogues of disoxaril, a broad spectrum antipicornavirus agent, have been prepared and evaluated against several rhinovirus serotypes. A QSAR study revealed that the mean MIC (MIC) against five rhinovirus serotypes correlated well with log P. The 2,6-dichloro analogue, 15, was highly effective in vitro against rhinoviruses with an MIC80 of 0.3 microM, as well as against several enteroviruses, and was also effective in preventing paralysis in mice infected with coxsackievirus A-9.
A variety of heterocyclic analogs of Win 54954 have been synthesized and tested in vitro against human rhinovirus type 14 (HRV-14) in a plaque reduction assay. The more active compounds were tested against 14 additional serotypes, and the concentration which inhibited 80% of the serotypes tested (MIC80) was measured. One compound, 37, exhibited activity comparable to Win 59454. Physicochemical as well as electrostatic parameters were calculated and the results subjected to a QSAR analysis in an effort to explain differences in activity observed between these compounds; however, no meaningful correlation with biological activity was found with any of these parameters.
Antipicornavirus Activity of Tetrazole Analogues Related to Disoxaril.-A series of tetrazole analogues, e.g. (II), of disoxaril (I) is synthesized and initially screened against human rhinovirus types 1A and 14 in a plaque reduction assay. Especially the compound (IIb) is found to be highly active (0.2 µM) against at least 15 rhinovirus serotypes. -(DIANA, G. D.; CUTCLIFFE, D.; VOLKOTS, D. L.; MALLAMO, J. P.; BAILEY, T. R.; VESCIO, N.; OGLESBY, R. C.; NITZ, T. J.; WETZEL, J.; GIRANDA, V.; PEVEAR, D. C.; DUTKO, F. J.; J. Med. Chem. 36 (1993) 22, 3240-3250; Sterling Winthrop Pharm. Res. Div., Collegeville, PA 19426, USA; EN)
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