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ID: ALA1157487

Journal: Bioorg Med Chem

Title: Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines.

Authors: Yokoyama K, Ishikawa N, Igarashi S, Kawano N, Hattori K, Miyazaki T, Ogino S, Matsumoto Y, Takeuchi M, Ohta M.

Abstract: A new series of quinazolines that function as CCR4 antagonists were discovered during the screening of our corporate compound libraries. Subsequent compound optimization elucidated the structure-activity relationships and led the identification of 2-(1,4'-bipiperidine-1'-yl)-N-cycloheptyl-6,7-dimethoxyquinazolin-4-amine 14a, which showed potent inhibition in the [(35)S]GTPgammaS-binding assay (IC(50)=18nM). This compound also inhibited the chemotaxis of human and mouse CCR4-expressing cells (IC(50)=140nM, 39nM).

CiteXplore: 18539035

DOI: 10.1016/j.bmc.2008.05.036