Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists
| Autor: | Keiko Suzuki, Ippei Sato, Makoto Takeuchi, Tatsuaki Morokata, Kazuki Ohno, Yosuke Iura, Koichiro Morihira, Hirokazu Kubota, Hiroshi Inami, Toshiya Takahashi, Mitsuaki Ohta, Takayuki Imaoka, Aiko Nitta, Shin-ichi Tsukamoto |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.drug_class
Stereochemistry Receptors CCR3 Clinical Biochemistry Pharmaceutical Science Carboxamide Naphthalenes Biochemistry Chemical synthesis chemistry.chemical_compound Mice Piperidines Drug Discovery Acetamides Anti-Allergic Agents medicine Animals Humans Protein Isoforms Phenols Molecular Biology Acrylamides Organic Chemistry Antagonist Haplorhini In vitro chemistry Acrylamide Microsome Microsomes Liver Molecular Medicine Thermodynamics Acetamide |
| Zdroj: | Bioorganicmedicinal chemistry. 17(16) |
| ISSN: | 1464-3391 |
| Popis: | Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CLint; mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-[1-(2-hydroxybenzoyl)piperidin-4-ylidene]acetamide (30j) was found to be a potent inhibitor (IC50 = 8.4 nM) with a high metabolic stability against HLMs. |
| Databáze: | OpenAIRE |
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