The discovery of BMS-457, a potent and selective CCR1 antagonist
Daniel S Gardner1, Joseph B Santella, John V Duncia
1Bristol-Myers Squibb Company, R&D, P.O. Box 4000, Princeton, NJ 08543-4000, USA. daniel.gardner@bms.com
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.
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