Synthesis and evaluation of novel ligands for the histamine H₄ receptor based on a pyrrolo[2,3-d]pyrimidine scaffold.

Starting from a known H(4)R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K(i)=0.5 μM), its lacks selectivity with a K(i) value for the hH(3)R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K(i) values of less than 1 μM at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands.