Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4509-14. doi: 10.1016/j.bmcl.2009.02.089. Epub 2009 Feb 27.

Abstract

Many years of work have been invested in the identification of potent and selective COX-2 inhibitors for the treatment of chronic inflammatory pain. One issue faced by workers is the balance between the lipophilicity required for potent enzyme inhibition and the physical properties necessary for drug absorption and distribution in vivo. Frequently approaches to reduce lipophilicity through introduction of polar functionality is hampered by highly challenging chemistry to prepare key molecules. We have complemented traditional synthetic chemistry with a biotransformations approach which efficiently provided access to an array of key target molecules.

MeSH terms

  • Biotransformation
  • Chemistry, Pharmaceutical / methods
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Drug Design
  • Humans
  • Inflammation / drug therapy
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2