Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl)azoles as potent CXCR3 antagonists

Development of a lead series of piperidinylurea CXCR3 antagonists has led to the identification of molecules with alternative linkages, which retain good potency. A piperidinyl thiadiazole derivative was found to have satisfactory in vitro metabolic stability and to be orally bioavailable in mice, giving high plasma concentrations and a half life of 5.4 h.