Lead identification and optimization of diaminopyrimidines as histamine H4 receptor ligands

Zusammenfassung

The human histamine H-4 receptor (hH(4)R) is a promising new target in the therapy of inflammatory or immune system diseases. For the development of new hH(4)R ligands, a broad virtual screening was performed and two hits were identified. Their annelated heterocyclic core was optimized with regard to affinity and potency. Pharmacological characterization of the resulting diaminopyrimidines revealed different agonist and antagonist properties within the same scaffold.