Role of the Hydrogen Bonding Heteroatom-Lys53 Interaction between the p38α Mitogen-Activated Protein (MAP) Kinase and Pyridinyl-Substituted 5-Membered Heterocyclic Ring Inhibitors

In the framework of Investigating the role of heteroatoms in pyridinyl-substituted 5-membered (hetero)cycles as potential p38 alpha MAP kinase inhibitor scaffolds, cyclopentene, pyrrole, furan, and imidazole analogues were synthesized and tested with respect to their ability to inhibit p38a MAP kinase. The vicinal pyridine/4-fluorophenyl pharmacophore was conserved, such as in the prototypical imidazole inhibitor SB203580. The strength of the HB interaction was calculated and compared to the biological data.