A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors

C S Li; W C Black; C Brideau; C C Chan; S Charleson; W A Cromlish; D Claveau; J Y Gauthier; R Gordon; G Greig; E Grimm; J Guay; C K Lau; D Riendeau; M Thérien; D M Visco; E Wong; L Xu; P Prasit

doi:10.1016/s0960-894x(99)00559-4

A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors

Bioorg Med Chem Lett. 1999 Nov 15;9(22):3181-6. doi: 10.1016/s0960-894x(99)00559-4.

Authors

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, Pointe-Clarie-Dorval, Quebec, Canada.

PMID: 10576684
DOI: 10.1016/s0960-894x(99)00559-4

Abstract

By inserting an oxygen link between the 3-fluorophenyl and the lactone ring of 5,5-dimethyl-3-(3fluorophenyl)-4-(4-methanesulfonylphenyl)-2 (5H)-furanone 1 (DFU), analogs with enhanced in vitro COX-2 inhibitory potency as well as in vivo potency in models of inflammation were obtained.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
CHO Cells
Cricetinae
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemistry*
Cyclooxygenase Inhibitors / pharmacokinetics
Cyclooxygenase Inhibitors / pharmacology
Furans / chemistry*
Furans / pharmacokinetics
Furans / pharmacology
Isoenzymes / drug effects*
Prostaglandin-Endoperoxide Synthases / drug effects*
Rats
Structure-Activity Relationship

Substances

5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone
Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Furans
Isoenzymes
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases