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Adhesion of pathogenic organisms to host tissues is the initiation of the majority of infectious diseases. It is often mediated by lectins present on the surface of infectious organisms which then combine with complementary sugars on the host surface.[1] One of the best characterized bacterial lectin involved in receptor-ligand interaction is mannose-specific type 1 fimbrial FimH adhesin. For example, in uropathogenic E. coli (UPEC) mannose-specific adhesion is mediated by this lectin.[2] A large number of α-D-mannopyranosides with aromatic aglycon moiety were found to bind with high affinity to FimH and thus prevent agglutination of red blood cells. In our previous work we have explored the inhibitory potential of α- mannosides with meta and para substituted N- aryl 3-hydroxy-2-methylpyridin-4-ones as aglycon parts of a molecule.[3, 4] The hemagglutination assays revealed greater preference of FimH towards the para substituted pyridinone mannosides. In this work we report the synthesis of novel para substituted N-aryl 3-hydroxypyridin-4-ones without methyl group in position 2 of the pyridinone ring (Figure). Their inhibitory properties towards the adhesion of E. coli to quinea pig erythrocytes will be evaluated using hemagglutination assay. These results will be compared with inhibitory potencies of analogous para derivatives of N- aryl 3-hydroxy 2-methylpyridin-4-ones. Computational analysis complemented experimental results by elucidating specific interactions within the FimH active site responsible for the binding and aided in the interpretation of the observed binding trends.