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PDBsum entry 3ws8
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Hydrolase/hydrolase inhibitor
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PDB id
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3ws8
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References listed in PDB file
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Key reference
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Title
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Novel benzimidazole derivatives as phosphodiesterase 10a (pde10a) inhibitors with improved metabolic stability.
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Authors
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A.Chino,
N.Masuda,
Y.Amano,
K.Honbou,
T.Mihara,
M.Yamazaki,
M.Tomishima.
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Ref.
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Bioorg Med Chem Lett, 2014,
22,
3515-3526.
[DOI no: ]
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PubMed id
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Abstract
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In this study, we report the identification of potent benzimidazoles as PDE10A
inhibitors. We first identified imidazopyridine 1 as a high-throughput screening
hit compound from an in-house library. Next, optimization of the imidazopyridine
moiety to improve inhibitory activity gave imidazopyridinone 10b. Following
further structure-activity relationship development by reducing lipophilicity
and introducing substituents, we acquired 35, which exhibited both improved
metabolic stability and reduced CYP3A4 time-dependent inhibition.
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