1.
Bioorg Med Chem Lett
; 14(22): 5537-42, 2004 Nov 15.
Article
in English
| MEDLINE
| ID: mdl-15482919
ABSTRACT
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.
Subject(s)
Lactams/chemistry , Lactams/pharmacokinetics , Receptors, Chemokine/antagonists & inhibitors , Animals , Binding Sites , Binding, Competitive/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical , Hypersensitivity/drug therapy , Lactams/chemical synthesis , Mice , Molecular Structure , Receptors, CCR4 , Stereoisomerism , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 14(7): 1619-24, 2004 Apr 05.
Article
in English
| MEDLINE
| ID: mdl-15026036
ABSTRACT
Substituted thiazolidinones were identified as CCR4 antagonists from high throughput screening. Subsequent lead optimization efforts resulted in defined structure-activity relationships and the identification of potent antagonists (compounds 90 and 91) that inhibited the chemotaxis of Th2 T-cells in vitro.
