SAR in the alkoxy lactone series: the discovery of DFP, a potent and orally active COX-2 inhibitor

Y Leblanc; P Roy; S Boyce; C Brideau; C C Chan; S Charleson; R Gordon; E Grimm; J Guay; S Léger; C S Li; D Riendeau; D Visco; Z Wang; J Webb; L J Xu; P Prasit

doi:10.1016/s0960-894x(99)00365-0

SAR in the alkoxy lactone series: the discovery of DFP, a potent and orally active COX-2 inhibitor

Bioorg Med Chem Lett. 1999 Aug 2;9(15):2207-12. doi: 10.1016/s0960-894x(99)00365-0.

Authors

Y Leblanc¹, P Roy, S Boyce, C Brideau, C C Chan, S Charleson, R Gordon, E Grimm, J Guay, S Léger, C S Li, D Riendeau, D Visco, Z Wang, J Webb, L J Xu, P Prasit

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, Québec, Canada.

PMID: 10465547
DOI: 10.1016/s0960-894x(99)00365-0

Abstract

Extensive SAR has been established in the alkoxy lactone series and this has lead to the discovery of DFP (5,5-dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanon e), a potent COX-2 inhibitor exhibiting in vivo efficacy in all models studied.

MeSH terms

Administration, Oral
Animals
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacokinetics
Cyclooxygenase Inhibitors / pharmacology
Humans
Isoenzymes / drug effects
Isoenzymes / metabolism*
Macaca mulatta
Membrane Proteins
Prostaglandin-Endoperoxide Synthases / drug effects
Prostaglandin-Endoperoxide Synthases / metabolism*
Rats
Saimiri
Structure-Activity Relationship
U937 Cells

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Membrane Proteins
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases