Discovery of DF-461, a Potent Squalene Synthase Inhibitor.

@article{Ichikawa2013DiscoveryOD,
  title={Discovery of DF-461, a Potent Squalene Synthase Inhibitor.},
  author={Masanori Ichikawa and Masami Ohtsuka and H. Ohki and M. Ota and Noriyasu Haginoya and M. Itoh and Y. Shibata and Yutaka Ishigai and K. Terayama and Akira Kanda and K. Sugita},
  journal={ACS medicinal chemistry letters},
  year={2013},
  volume={4 10},
  pages={
          932-6
        }
}
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. 
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  • 165
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  • 33
  • PDF
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  • 2
  • PDF
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  • 74
...
1
2
...

References

SHOWING 1-10 OF 20 REFERENCES
Discovery of novel tricyclic compounds as squalene synthase inhibitors.
  • 16
Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors.
  • 13
Synthesis and activity of a novel series of 3-biarylquinuclidine squalene synthase inhibitors.
  • 53
Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors
  • J. Tobert
  • Medicine
  • Nature Reviews Drug Discovery
  • 2003
  • 652
  • PDF
...
1
2
...