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ID: ALA4339202

Journal: Bioorg Med Chem Lett

Title: Benzothiophene derivatives as phosphodiesterase 10A (PDE10A) inhibitors: Hit-to-lead studies.

Authors: Kawamoto Y, Tomino M, Hiramatsu K, Oyama Y, Hayashi Y.

Abstract: A novel series of benzothiophene derivatives was discovered as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity relationship studies on high-throughput screening hit compound 1 led to the identification of 7-acetyl-3-methyl-N-(quinolin-2-yl)-1-benzothiophene-2-carboxamide (16), with potent inhibitory activity (PDE10A IC50 = 7.6 nM) and selectivity (>1300-fold selectivity over the other tested phosphodiesterases). In addition, a novel methyl-induced conformational alteration of the benzothiophene-2-carboxamide derivatives is reported.

CiteXplore: 30952590

DOI: 10.1016/j.bmcl.2019.03.021