2. Academic Validation
  3. Discovery of DF-461, a Potent Squalene Synthase Inhibitor

Discovery of DF-461, a Potent Squalene Synthase Inhibitor

  • ACS Med Chem Lett. 2013 Sep 4;4(10):932-6. doi: 10.1021/ml400151c.
Masanori Ichikawa 1,  Masami Ohtsuka 1,  Hitoshi Ohki 1,  Masahiro Ota 1,  Noriyasu Haginoya 1,  Masao Itoh 1,  Yoshihiro Shibata 1,  Yutaka Ishigai 1,  Koji Terayama,  Akira Kanda 1,  Kazuyuki Sugita 1
Affiliations

Affiliation

  • 1 R&D Division, Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 24900587 DOI: 10.1021/ml400151c
Abstract

We report the development of a new trifluoromethyltriazolobenzoxazepine series of squalene synthase inhibitors. Structure-activity studies and pharmacokinetics optimization on this series led to the identification of compound 23 (DF-461), which exhibited potent squalene synthase inhibitory activity, high hepatic selectivity, excellent rat hepatic Cholesterol synthesis inhibitory activity, and plasma lipid lowering efficacy in nonrodent repeated dose studies.

Keywords

Squalene synthase; dyslipidemia; inhibitor; triazolobenzoxazepine.

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