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

  • Bioorg Med Chem Lett. 2013 Jul 1;23(13):3833-40. doi: 10.1016/j.bmcl.2013.04.079.
Daniel S Gardner  1 ,  Joseph B Santella 3rd ,  John V Duncia ,  Percy H Carter ,  T G Murali Dhar ,  Hong Wu ,  Weiwei Guo ,  Cullen Cavallaro ,  Katy Van Kirk ,  Melissa Yarde ,  Stephanie W Briceno ,  R Robert Grafstrom ,  Richard Liu ,  Sima R Patel ,  Andrew J Tebben ,  Dan Camac ,  Javed Khan ,  Andrew Watson ,  Guchen Yang ,  Anne Rose ,  William R Foster ,  Mary Ellen Cvijic ,  Paul Davies ,  John Hynes Jr
Affiliations
  • 1. Bristol-Myers Squibb Company, R&D, P.O. Box 4000, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 23707259 DOI: 10.1016/j.bmcl.2013.04.079
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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