Novel amide and imidazole compounds as potent hematopoietic prostaglandin D synthase inhibitors.

In seeking novel and potent small molecule hematopoietic prostaglandin D synthase (H-PGDS) inhibitors as potential therapies for PGD-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole "linker" between the pyrimidine or pyridine "core" ring and the "tail" ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD stimulation.