Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition |
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Authors: | Wataru Hamaguchi Naoyuki Masuda Mai Isomura Satoshi Miyamoto Shigetoshi Kikuchi Yasushi Amano Kazuya Honbou Takuma Mihara Toshihiro Watanabe |
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Affiliation: | Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan |
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Abstract: | 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. |
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Keywords: | PDE10A inhibitor Schizophrenia Benzimidazole CYP1A2 |
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