Urea based CCR3 antagonists employing a tetrahydro-1,3-oxazin-2-one spacer

  • Bioorg Med Chem Lett. 2009 Jan 1;19(1):96-9. doi: 10.1016/j.bmcl.2008.11.002.
T G Murali Dhar  1 ,  Guchen Yang ,  Paul Davies ,  Mary F Malley ,  Jack Z Gougoutas ,  Dauh-Rurng Wu ,  Joel C Barrish ,  Percy H Carter
Affiliations
  • 1. Bristol-Myers Squibb Company, Research and Development, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 19010676 DOI: 10.1016/j.bmcl.2008.11.002
Abstract

Conformational restriction of open chain analogs with a more polar tetrahydro-1,3-oxazin-2-one spacer led to the identification of potent urea-based CCR3 antagonists that exhibited excellent selectivity over binding to CYP2D6. The in vitro binding and eosinophil shape change data are presented. Compound 19b exhibited similar selectivity and potency to our development candidate BMS-639623.