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

T G Murali Dhar; Guchen Yang; Paul Davies; Mary F Malley; Jack Z Gougoutas; Dauh-Rurng Wu; Joel C Barrish; Percy H Carter

doi:10.1016/j.bmcl.2008.11.002

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. Epub 2008 Nov 6.

Authors

T G Murali Dhar¹, Guchen Yang, Paul Davies, Mary F Malley, Jack Z Gougoutas, Dauh-Rurng Wu, Joel C Barrish, Percy H Carter

Affiliation

¹ Bristol-Myers Squibb Company, Research and Development, Princeton, NJ 08543-4000, USA. murali.dhar@bms.com

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.

MeSH terms

Cell Shape / drug effects
Cytochrome P-450 CYP2D6 / drug effects
Eosinophils / cytology
Eosinophils / drug effects
Humans
Molecular Structure
Piperidines
Protein Binding
Receptors, CCR3 / antagonists & inhibitors*
Structure-Activity Relationship
Urea / analogs & derivatives
Urea / chemistry*
Urea / pharmacology

Substances

BMS-639623
Piperidines
Receptors, CCR3
Urea
Cytochrome P-450 CYP2D6