Abstract
The preparation of the sulfoxide analogues 2 and 4, and their enantiomeric pure forms is discussed as well as their potential to act as prodrugs to the potent and selective sulfone-containing COX-2 inhibitors rofecoxib and etoricoxib. Sulfoxides 2 and 4 were shown to be effectively transformed in vivo into rofecoxib and etoricoxib, respectively, after oral administration in rats. In the case of sulfoxide 2, both a slightly improved pharmacokinetic profile and a better pharmacological activity in an arthritis model were seen when compared with rofecoxib.
MeSH terms
-
Animals
-
Cyclooxygenase 2 / metabolism
-
Cyclooxygenase 2 Inhibitors / blood
-
Cyclooxygenase 2 Inhibitors / chemical synthesis
-
Cyclooxygenase 2 Inhibitors / chemistry
-
Cyclooxygenase 2 Inhibitors / pharmacology*
-
Etoricoxib
-
Humans
-
Isomerism
-
Lactones / blood
-
Lactones / chemical synthesis
-
Lactones / chemistry*
-
Lactones / pharmacology*
-
Male
-
Molecular Structure
-
Prodrugs / chemical synthesis
-
Prodrugs / chemistry
-
Prodrugs / pharmacokinetics
-
Prodrugs / pharmacology*
-
Pyridines / blood
-
Pyridines / chemical synthesis
-
Pyridines / chemistry*
-
Pyridines / pharmacology*
-
Rats
-
Rats, Wistar
-
Safrole / analogs & derivatives*
-
Safrole / chemistry
-
Solubility
-
Sulfones / blood
-
Sulfones / chemical synthesis
-
Sulfones / chemistry*
-
Sulfones / pharmacology*
-
Temperature
-
Thermodynamics
Substances
-
Cyclooxygenase 2 Inhibitors
-
Lactones
-
Prodrugs
-
Pyridines
-
Sulfones
-
rofecoxib
-
Cyclooxygenase 2
-
Safrole
-
sulfoxide
-
Etoricoxib