Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders
Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key
Comparison of N,N′-diarylsquaramides and N,N′-diarylureas as antagonists of the CXCR2 chemokine receptor
N,N′-diarylsquaramides were prepared and evaluated as antagonists of CXCR2. The compounds were found to be potent and selective antagonists of CXCR2. Significant differences in SAR was observed relative to the previously described N,N′-diarylurea series. As was the case in the N,N′-diarylurea series, placing sulfonamide substituent adjacent to the acidic phenol significantly reduced the clearance in rat pharmacokinetic studies.
McCleland, Brent W.,Davis, Roderick S.,Palovich, Michael R.,Widdowson, Katherine L.,Werner, Michelle L.,Burman, Miriam,Foley, James J.,Schmidt, Dulcie B.,Sarau, Henry M.,Rogers, Martin,Salyers, Kevin L.,Gorycki, Peter D.,Roethke, Theresa J.,Stelman, Gary J.,Azzarano, Leonard M.,Ward, Keith W.,Busch-Petersen, Jakob
p. 1713 - 1717
(2007/10/03)
More Articles about upstream products of 934275-43-1