Oxidosqualene Cyclase (OSC) Inhibitors for the Treatment of Dyslipidemia

Authors

  • Henrietta Dehmlow
  • Ralf Thoma
  • Armin Ruf
  • Narendra Panday
  • Elisabeth Von Der Mark
  • Olivier Morand
  • Hans Peter Märki
  • Manfred Kansy
  • Peter Hartman
  • Philippe Coassolo
  • Alexander Chucholowski
  • Denise Blum-Kaelin
  • Johannes Aebi
  • Jean Ackermann
  • Tanja Schulz-Gasch

DOI:

https://doi.org/10.2533/000942905777676858

Keywords:

Dyslipidemia, Medicinal chemistry, Oxidosqualene cyclase, Structure-activity relationship

Abstract

Novel inhibitors of oxidosqualene cyclase (OSC) for the treatment of dyslipidemia are reported. Starting point for the chemistry program was a set of compounds derived from a fungicide project which, in addition to high affinity for OSC from Candida albicans, also showed high affinity for the human enzyme (hOSC). Here the evaluation process of different scaffolds is outlined for two representative series, the phenyl substituted benzo[d]isothiazoles and the aminocyclohexanes. The most promising compounds derived from the latter series were further profiled in vivo and showed promising properties with respect to modulation of lipid parameters.

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Published

2005-03-01