Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists.
A series of racemic and chiral, nonracemic lactams that display high binding affinities, functional chemotaxis antagonism, and selectivity toward CCR4 are described. Compound 41, which provides reasonably high blood levels in mice when dosed intraperitoneally, was identified as a useful pharmacological tool to explore the role of CCR4 antagonism in animal models of allergic disease.
Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA.
Bradley
B
Newhouse
Shelley
S
Allen
Benjamin
B
Fauber
Aaron S
AS
Anderson
C Todd
CT
Eary
Joshua D
JD
Hansen
Justin
J
Schiro
John J
JJ
Gaudino
Ellen
E
Laird
David
D
Chantry
Christine
C
Eberhardt
Laurence E
LE
Burgess
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006967:Hypersensitivity / Q000188:drug therapy; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D015394:Molecular Structure; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C515355:Ccr4 protein, mouse; D007769:Lactams; D054398:Receptors, CCR4; D019707:Receptors, Chemokine