Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors

C K Lau; C Brideau; C C Chan; S Charleson; W A Cromlish; D Ethier; J Y Gauthier; R Gordon; J Guay; S Kargman; C S Li; P Prasit; D Riendeau; M Thérien; D M Visco; L Xu

doi:10.1016/s0960-894x(99)00560-0

Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors

Bioorg Med Chem Lett. 1999 Nov 15;9(22):3187-92. doi: 10.1016/s0960-894x(99)00560-0.

Authors

C K Lau¹, C Brideau, C C Chan, S Charleson, W A Cromlish, D Ethier, J Y Gauthier, R Gordon, J Guay, S Kargman, C S Li, P Prasit, D Riendeau, M Thérien, D M Visco, L Xu

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Québec, Canada.

PMID: 10576685
DOI: 10.1016/s0960-894x(99)00560-0

Abstract

A series of 3-heteroaryloxy4-phenyl-2-5H)-furanones were prepared and evaluated for their potency and selectivity as COX-2 inhibitors. This led to the identification of L-778,736 as a potent, orally active and selective inhibitor of the COX-2 enzyme.

MeSH terms

Animals
Biological Availability
CHO Cells
Cricetinae
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / pharmacokinetics
Cyclooxygenase Inhibitors / pharmacology*
Furans / chemical synthesis*
Furans / pharmacokinetics
Furans / pharmacology*
Humans
Isoenzymes / drug effects*
Membrane Proteins
Prostaglandin-Endoperoxide Synthases / drug effects*
Pyridines / chemical synthesis
Pyridines / pharmacokinetics
Pyridines / pharmacology
Rats

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Furans
Isoenzymes
L 778736
Membrane Proteins
Pyridines
Cyclooxygenase 2
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases