1. Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.
- Author
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Santella JB 3rd, Gardner DS, Duncia JV, Wu H, Dhar M, Cavallaro C, Tebben AJ, Carter PH, Barrish JC, Yarde M, Briceno SW, Cvijic ME, Grafstrom RR, Liu R, Patel SR, Watson AJ, Yang G, Rose AV, Vickery RD, Caceres-Cortes J, Caporuscio C, Camac DM, Khan JA, An Y, Foster WR, Davies P, and Hynes J Jr
- Subjects
- Animals, Biological Availability, Clinical Trials, Phase II as Topic, Hep G2 Cells, Humans, Male, Microsomes, Liver metabolism, Models, Molecular, Piperidines metabolism, Piperidines pharmacokinetics, Piperidines therapeutic use, Pregnane X Receptor, Protein Conformation, Receptors, CCR1 chemistry, Receptors, CCR1 metabolism, Receptors, Steroid metabolism, Species Specificity, Urea metabolism, Urea pharmacokinetics, Urea pharmacology, Urea therapeutic use, Valine metabolism, Valine pharmacokinetics, Valine pharmacology, Valine therapeutic use, Arthritis, Rheumatoid drug therapy, Drug Discovery, Piperidines pharmacology, Receptors, CCR1 antagonists & inhibitors, Urea analogs & derivatives, Valine analogs & derivatives
- Abstract
High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
- Published
- 2014
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