Medicinal Chemistry Research

, Volume 16, Issue 3, pp 119–129

Synthesis and pharmacological evaluation of m-terphenyl amines as cyclooxygenase inhibitors

Authors

  • John D. Bauer
    • College of Pharmacy and Health SciencesMercer University
  • Michael S. Foster
    • School of Chemistry and BiochemistryGeorgia Institute of Technology
  • Jeffrey D. Hugdahl
    • Department of Chemistry, College of Liberal ArtsMercer University
  • Kristi L. Burns
    • School of Chemistry and BiochemistryGeorgia Institute of Technology
  • Sheldon W. May
    • School of Chemistry and BiochemistryGeorgia Institute of Technology
  • Stanley H. Pollock
    • College of Pharmacy and Health SciencesMercer University
  • Horace G. Cutler
    • College of Pharmacy and Health SciencesMercer University
    • Department of Medicinal Chemistry, School of PharmacyThe University of Mississippi
Original Research

DOI: 10.1007/s00044-007-9015-x

Cite this article as:
Bauer, J.D., Foster, M.S., Hugdahl, J.D. et al. Med Chem Res (2007) 16: 119. doi:10.1007/s00044-007-9015-x

Abstract

A series of m-terphenyl amines was synthesized and evaluated as a novel class of cyclooxygenase (COX) inhibitors. Structure–activity relationships (SAR) were investigated by functional group modification at the para-position of the C-1′ and C-2′ phenyl substituents on the central aromatic ring. Anilines 6a, b, d, and h demonstrated nonselective inhibition of COX-1 and -2 in human whole blood. Compounds 6c and e demonstrated preferential inhibition of the COX-2 isozyme at 10 μM. Molecules 6f, i, and j inhibited only COX-1, and the disubstituted ethoxy derivative (6g) was inactive as a COX inhibitor (≤ 100 μM). Molecular docking studies of these compounds indicate that the COX-1 binding site amino acid Ile523 anchors the m-terphenyl system statically within the enzyme’s active site, while the slightly smaller amino acid Val523 in COX-2 allows the ligand to “roll,” fashioning several acceptable conformers.

Copyright information

© Birkha¨user Boston 2007