2. Academic Validation
  3. Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines

Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines

  • Bioorg Med Chem. 2009 Jan 1;17(1):64-73. doi: 10.1016/j.bmc.2008.11.020.
Kazuhiro Yokoyama 1,  Noriko Ishikawa,  Susumu Igarashi,  Noriyuki Kawano,  Naoyuki Masuda,  Wataru Hamaguchi,  Shingo Yamasaki,  Yohei Koganemaru,  Kazuyuki Hattori,  Takahiro Miyazaki,  Shin-Ichi Ogino,  Yuzo Matsumoto,  Makoto Takeuchi,  Mitsuaki Ohta
Affiliations

Affiliation

  • 1 Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. [email protected]
PMID: 19081254 DOI: 10.1016/j.bmc.2008.11.020
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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