Design and synthesis of pyrimido[4,5-b][1,4]benzothiazine derivatives, as potent 15-lipoxygenase inhibitors

  • Bioorg Med Chem. 2007 Mar 1;15(5):2120-6. doi: 10.1016/j.bmc.2006.12.022.
M Bakavoli  1 ,  M Nikpour ,  M Rahimizadeh ,  M R Saberi ,  H Sadeghian
Affiliations
  • 1. Department of Chemistry, School of Sciences, Ferdowsi University, Mashhad 91775-1436, Iran. [email protected]
PMID: 17210254 DOI: 10.1016/j.bmc.2006.12.022
Abstract

A group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines were designed, synthesized, and evaluated as potential inhibitors of 15-lipoxygenase (15-LO). Compounds 4d and 4e showed the best IC50 of 15-LO inhibition (IC50=18 and 34 microM, respectively). All compounds were docked into 15-LO. As a result the sulfur atom was oriented toward the iron atom of the active site of 15-LO. We suggest the interaction of the iron atom is essential for the activity of the inhibitors.

Products