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

M Ichikawa, A Yokomizo, M Itoh, N Haginoya…

Index: Ichikawa, Masanori; Yokomizo, Aki; Itoh, Masao; Haginoya, Noriyasu; Sugita, Kazuyuki; Usui, Hiroyuki; Terayama, Koji; Kanda, Akira Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 17 p. 5207 - 5224

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Citation Number: 7

Abstract

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 ...