Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition
| Autor: | Kazuya Honbou, Shigetoshi Kikuchi, Takuma Mihara, Naoyuki Masuda, Mai Isomura, Wataru Hamaguchi, Satoshi Miyamoto, Yasushi Amano, Toshihiro Watanabe |
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| Rok vydání: | 2013 |
| Předmět: |
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Molecular Benzimidazole Cytochrome P-450 CYP1A2 Inhibitors Phosphodiesterase Inhibitors Stereochemistry Clinical Biochemistry Pharmaceutical Science Crystallography X-Ray Ring (chemistry) Biochemistry Structure-Activity Relationship chemistry.chemical_compound Cytochrome P-450 CYP1A2 Drug Discovery Humans Molecular Biology Dose-Response Relationship Drug Molecular Structure Phosphoric Diester Hydrolases Organic Chemistry Quinoline CYP1A2 Phosphodiesterase Recombinant Proteins chemistry Drug Design Molecular Medicine Benzimidazoles PDE10A Lead compound Isopropyl |
| Zdroj: | Bioorganic & Medicinal Chemistry. 21:7612-7623 |
| ISSN: | 0968-0896 |
| Popis: | A novel class of phosphodiesterase 10A (PDE10A) inhibitors with reduced CYP1A2 inhibition were designed and synthesized starting from 2-{[(1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (1). Introduction of an isopropyl group at the 2-position and a methoxy group at the 5-position of the benzimidazole ring of lead compound 1 resulted in the identification of 2-{[(2-isopropyl-5-methoxy-1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (25b), which exhibited potent PDE10A inhibitory activity with reduced CYP1A2 inhibitory activity compared to compound 1. |
| Databáze: | OpenAIRE |
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