Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists

Bradley Newhouse; Shelley Allen; Benjamin Fauber; Aaron S Anderson; C Todd Eary; Joshua D Hansen; Justin Schiro; John J Gaudino; Ellen Laird; David Chantry; Christine Eberhardt; Laurence E Burgess

doi:10.1016/j.bmcl.2004.09.001

Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5537-42. doi: 10.1016/j.bmcl.2004.09.001.

Authors

Bradley Newhouse¹, Shelley Allen, Benjamin Fauber, Aaron S Anderson, C Todd Eary, Joshua D Hansen, Justin Schiro, John J Gaudino, Ellen Laird, David Chantry, Christine Eberhardt, Laurence E Burgess

Affiliation

¹ Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA.

PMID: 15482919
DOI: 10.1016/j.bmcl.2004.09.001

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.

MeSH terms

Animals
Binding Sites
Binding, Competitive / drug effects
Disease Models, Animal
Drug Evaluation, Preclinical
Hypersensitivity / drug therapy
Lactams / chemical synthesis
Lactams / chemistry*
Lactams / pharmacokinetics*
Mice
Molecular Structure
Receptors, CCR4
Receptors, Chemokine / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship

Substances

Ccr4 protein, mouse
Lactams
Receptors, CCR4
Receptors, Chemokine