Structural alterations of the aglycon portions of α‐mannosides influence their inhibitory potency toward type 1‐fimbriated Escherichia coli. The aim of our work was to prepare and explore inhibitory properties of novel mannosylated N‐aryl‐substituted 3‐hydroxypyridine‐4‐ones because they possess needed structural characteristics as possible FimH antagonists. Hemagglutination inhibitory tests showed that the examined 3‐hydroxypyridine‐4‐one α‐mannosides exhibited better inhibitory activity than methyl α‐d‐mannopyranoside used as a reference compound. Molecular modeling studies revealed the specific interactions responsible for the observed binding activities toward the mannose‐specific FimH lectin. The activity depends on the substituent in p‐position on the aglycon aromatic ring.