Discovery of atrop fixed alkoxy-aminobenzhydrol derivatives: novel, highly potent and orally efficacious squalene synthase inhibitors.

Basic Information

ID: ALA1817583

Journal: Bioorg Med Chem

Title: Discovery of atrop fixed alkoxy-aminobenzhydrol derivatives: novel, highly potent and orally efficacious squalene synthase inhibitors.

Authors: Ichikawa M, Yokomizo A, Itoh M, Haginoya N, Sugita K, Usui H, Terayama K, Kanda A.

Abstract: We have recently reported the discovery of the new benzhydrol template, which has a highly potent inhibitory activity for squalene synthase, as typified by compound 1 (SSI IC(50)=0.85 nM). However, it was composed of a pair of easy rotatable atropisomers. In the effort to fix the isomerization, a highly potent alkoxy-aminobenzhydrol scaffold was developed. Some of these acquired compounds demonstrating strong cholesterol synthesis inhibitory activities in a rat hepatic cell. Moreover, two of the series compounds exhibited specific plasma lipid-lowering effects in in vivo animal models.

CiteXplore: 21802309

DOI: 10.1016/j.bmc.2011.07.007

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