4-aryl- and 4-arylthio-5-hydroxy-2(5H)-furanones as inhibitors of phospholipase A.sub.2

US5464865A · kind A · utility

Assignee

• Ortho Pharmaceutical Corporation · US

Inventors

• James P. Demers · New York, US
• Richard B. Sulsky · Somerville, US

Key dates

• Filing date: Dec 22, 1993
• Grant date: Nov 7, 1995
• Expiry date: Dec 22, 2013

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D417/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The invention provides novel 5-hydroxy-4-aryl- and 5-hydroxy-4-(arylthio)-2(5H)-furanones of the following structure: ##STR1## wherein R contains from about five to about twenty carbon atoms and is defined herein; X is oxygen, sulfur, SO.sub.2, NH, N(lower alkyl), N(lower acyl), aminocarbonyl, carbonyl, carbonylamino, CH.sub.2 or a carbon-carbon bond; Y is hydrogen, halogen, lower alkyl, nitro, alkylthio, perfluoroalkyl, hydroxy, or lower alkoxy(C.sub.1 -C.sub.8); Z is sulfur or a carbon-carbon bond; and Q is H, an alkyl of from 1-20 carbon atoms, COR', COOR', CONHR', PO(OR')2, PO(OR')R" wherein R' and R" are independently selected from the group consisting of H, an alkyl of from 1-20 carbon atoms, phenyl, and substituted phenyl and prodrugs thereof and pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprising these compounds, methods of using these compounds as inhibitors of inflammation and for treating other diseases characterized by the overproduction of arachidonic acid metabolites, intermediates and methods of preparing these compounds are also provided.