A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these compounds exhibited mean MICs (MIC) against five serotypes as low as 0.40 microM. The mean MIC correlated well (r = 0.83) with the MIC80 (the concentration that inhibited 80% of the serotypes tested). A quantitative structure-activity relationship study indicated a strong dependency of MIC on lipophilicity (log P) in combination with inductive effects (sigma m) and bulk factors (MW).