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CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity |
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| Authors: | Pruitt James R Batt Douglas G Wacker Dean A Bostrom Lori L Booker Shon K McLaughlin Erin Houghton Gregory C Varnes Jeffrey G Christ David D Covington Maryanne Das Anuk M Davies Paul Graden Danielle Kariv Ilona Orlovsky Yevgeniya Stowell Nicole C Vaddi Krishna G Wadman Eric A Welch Patricia K Yeleswaram Swamy Solomon Kimberly A Newton Robert C Decicco Carl P Carter Percy H Ko Soo S |
| Affiliation: | Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. |
| Abstract: | DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2D6 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. |
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