Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit COX-1 and COX-2

Werner Seebacher; Johanna Faist; Armin Presser; Robert Weis; Robert Saf; Teresa Kaserer; Veronika Temml; Daniela Schuster; Sabine Ortmann; Nadine Otto; Rudolf Bauer

doi:10.1016/j.ejmech.2015.07.003

Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit COX-1 and COX-2

Eur J Med Chem. 2015 Aug 28:101:552-9. doi: 10.1016/j.ejmech.2015.07.003. Epub 2015 Jul 10.

Authors

Affiliations

¹ Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Universitätsplatz 1, 8010 Graz, Austria. Electronic address: we.seebacher@uni-graz.at.
² Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Universitätsplatz 1, 8010 Graz, Austria.
³ Institute for Chemistry and Technology of Organic Materials (ICTM), Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria.
⁴ Institute of Pharmacy, Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
⁵ Institute of Pharmacy, Pharmacognosy, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
⁶ Institute of Pharmaceutical Sciences, Pharmacognosy, University of Graz, Universitätsplatz 4, 8010 Graz, Austria.

PMID: 26197159
DOI: 10.1016/j.ejmech.2015.07.003

Abstract

Several new 4-phenylpyrimidine-2(1H)-thiones have been prepared and investigated for their potencies to inhibit COX-1 and COX-2 enzymes, and COX-2 expression in THP-1 cells. Structure-activity-relationships and physicochemical parameters are discussed. Pharmacophore screening and docking studies were carried out for the most active compound.

Keywords: 4-Phenylpyrimidine-2(1H)-thiones; Inhibition of cyclooxygenases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyclooxygenase 1 / metabolism*
Cyclooxygenase 2 / metabolism*
Cyclooxygenase Inhibitors / chemical synthesis
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Models, Molecular
Molecular Structure
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship
Thiones / chemical synthesis
Thiones / chemistry
Thiones / pharmacology*

Substances

Cyclooxygenase Inhibitors
Pyrimidines
Thiones
Cyclooxygenase 1
Cyclooxygenase 2