Urea based CCR3 antagonists employing a tetrahydro-1,3-oxazin-2-one spacer.
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.
Dhar
T G Murali
TG
Bristol-Myers Squibb Company, Research and Development, Princeton, NJ 08543-4000, USA. murali.dhar@bms.com
Yang
Guchen
G
Davies
Paul
P
Malley
Mary F
MF
Gougoutas
Jack Z
JZ
Wu
Dauh-Rurng
DR
Barrish
Joel C
JC
Carter
Percy H
PH
D048430:Cell Shape / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines; D011485:Protein Binding; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology
C528978:BMS-639623; D010880:Piperidines; D054397:Receptors, CCR3; D014508:Urea; D019389:Cytochrome P-450 CYP2D6