Potent and orally bioavailable CCR4 antagonists: Synthesis and structure–activity relationship study of 2-aminoquinazolines
| Autor: | Kazuyuki Hattori, Kazuhiro Yokoyama, Shin-Ichi Ogino, Yohei Koganemaru, Takahiro Miyazaki, Naoyuki Masuda, Yuzo Matsumoto, Mitsuaki Ohta, Noriko Ishikawa, Susumu Igarashi, Makoto Takeuchi, Wataru Hamaguchi, Noriyuki Kawano, Shingo Yamasaki |
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| Rok vydání: | 2009 |
| Předmět: |
Receptors
CCR4 Stereochemistry Clinical Biochemistry Anti-Inflammatory Agents Administration Oral Pharmaceutical Science Dermatitis Pharmacology Biochemistry Pyrrolidine Mice Structure-Activity Relationship chemistry.chemical_compound Piperidines Oral administration Drug Discovery Animals Humans Moiety Structure–activity relationship Potency Hydroxymethyl Amines Molecular Biology Chemistry Chemotaxis Organic Chemistry Disease Models Animal Quinazolines Molecular Medicine Piperidine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:64-73 |
| ISSN: | 0968-0896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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