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Updated: Jun 27, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of
Kazuhiro Yokoyama1, Noriko Ishikawa, Susumu Igarashi
1Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. kazuhiro.yokoyama@jp.astellas.com
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.
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