Document Report Card
Basic Information
ID: ALA1139358
Journal: Bioorg Med Chem
Title: Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines.
Authors: Yokoyama K, Ishikawa N, Igarashi S, Kawano N, Masuda N, Hamaguchi W, Yamasaki S, Koganemaru Y, Hattori K, Miyazaki T, Ogino S, Matsumoto Y, Takeuchi M, Ohta M.
Abstract: Starting with a series of CC chemokine receptor-4 (CCR4) antagonists developed in a previous study, the potency was improved by replacing the pyrrolidine moiety of N-(4-chlorophenyl)-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine 2 with a 3-(hydroxymethyl)piperidine. The resulting compound (1'-{4-[(4-chlorophenyl)amino]-6,7-dimethoxyquinazolin-2-yl}-1,4'-bipiperidin-3-yl)methanol 8ic was a strong inhibitor of human/mouse chemotaxis. Oral administration of 8ic showed anti-inflammatory activity in a murine model of acute dermatitis (oxazolone-induced contact hypersensitivity test) in a dose-dependent manner.
CiteXplore: 19081254