2. Academic Validation
  3. The discovery of BMS-457, a potent and selective CCR1 antagonist

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

Affiliation

  • 1 Bristol-Myers Squibb Company, R&D, P.O. Box 4000, Princeton, NJ 08543-4000, USA. daniel.gardner@bms.com
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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