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Design and synthesis of substituted imidazole and triazole N-phenylbenzo[d]oxazolamine inhibitors of retinoic acid metabolizing enzyme CYP26

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
  • Stephane Pautus
  • Ahmed S. Aboraia
  • Claire E. Bassett
  • Andrea Brancale
  • Michael Coogan
  • Claire Simons
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<mark>Journal publication date</mark>2009
<mark>Journal</mark>Journal of Enzyme Inhibition and Medicinal Chemistry
Issue number2
Volume24
Number of pages12
Pages (from-to)487-498
Publication StatusPublished
<mark>Original language</mark>English

Abstract

The design of N-phenylbenzo[d]oxazolamines as CYP26A1 inhibitors involved ligand docking experiments using molecular modeling (FlexX) and analysis of ligand interactions at the binding domain. The synthesis of the benzooxazol-2-yl-[phenyl-imidazol-1-yl-methyl)phenyl]amines was achieved by cyclisation of the corresponding isothiocyanates with subsequent introduction of the haem-binding heterocycle. Triazole and tetrazole derivatives were also prepared for comparison with the lead imidazole derivative. The benzooxazol-2-yl-[phenyl-imidazol-1-yl-methyl)phenyl]amines with small substituents in the phenyl ring were moderately potent CYP26A1 inhibitors (IC50 8 and 12 μM) and comparable with liarozole (IC50 7 μM).