Discovery of potent and specific CXCR3 antagonists

We previously reported CXCR3 clinical candidate compound, AMG 487. This Letter reported the efforts to discover the second generation of CXCR3 antagonist. From these efforts, compounds 25 is a much potent analog than AMG 487 with excellent bioavailability in multiple preclinical species and demonstrated efficacy in a mouse model of bleomycin-induced leukocytes trafficking into the lung.