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Basic Information

ID: ALA2396549

Journal: Bioorg Med Chem Lett

Title: The discovery of BMS-457, a potent and selective CCR1 antagonist.

Authors: Gardner DS, Santella JB, Duncia JV, Carter PH, Dhar TG, Wu H, Guo W, Cavallaro C, Van Kirk K, Yarde M, Briceno SW, Grafstrom RR, Liu R, Patel SR, Tebben AJ, Camac D, Khan J, Watson A, Yang G, Rose A, Foster WR, Cvijic ME, Davies P, Hynes J.

Abstract: A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.

CiteXplore: 23707259

DOI: 10.1016/j.bmcl.2013.04.079