Conformationally restricted 3,4-diarylfuranones (2,3a,4,5-tetrahydronaphthofuranones) as selective cyclooxygenase-2 inhibitors.

A number of naphthofuranones were synthesized and tested for COX-1 and COX-2 inhibition. Few of them were identified as selective COX-2 inhibitors. Structure-activity relationship studies within the series are discussed.

[1]  M. Pal,et al.  A simple and rapid entry to 5-alkyl (aryl)-5-hydroxy-3,4-diarylfuranones and 3a-hydroxy-1-aryl-2,3a, 4,5-tetrahydronaphthofuranones via a tandem esterification and oxidative cyclization process , 2002 .

[2]  D. Riendeau,et al.  A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors. , 1999, Bioorganic & medicinal chemistry letters.

[3]  D. Riendeau,et al.  SAR in the alkoxy lactone series: the discovery of DFP, a potent and orally active COX-2 inhibitor. , 1999, Bioorganic & medicinal chemistry letters.

[4]  M. A. Rahim,et al.  Isomeric acetoxy analogues of rofecoxib: a novel class of highly potent and selective cyclooxygenase-2 inhibitors. , 2002, Bioorganic & medicinal chemistry letters.

[5]  R Gordon,et al.  2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors. , 1998, Bioorganic & medicinal chemistry letters.

[6]  S. Higuchi,et al.  NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. , 1994, Prostaglandins.

[7]  R. S. Rogers,et al.  4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: a potent and selective inhibitor of COX-2. , 2000, Journal of medicinal chemistry.

[8]  J. Chow,et al.  Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2 , 1996, Nature Structural Biology.

[9]  D. Riendeau,et al.  Synthesis and biological evaluation of 5,6-diarylimidazo[2.1-b]thiazole as selective COX-2 inhibitors , 1997 .

[10]  P. Lipsky,et al.  Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. , 1998, Arthritis and rheumatism.

[11]  E. Knaus,et al.  Design and synthesis of celecoxib and rofecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: replacement of sulfonamide and methylsulfonyl pharmacophores by an azido bioisostere. , 2001, Journal of medicinal chemistry.

[12]  M. Pal,et al.  ChemInform Abstract: Synthesis of 3,4-Diarylsubstituted Maleic Anhydride/Maleimide via Unusual Oxidative Cyclization of Phenacyl Ester/Amide. , 2002 .

[13]  H Perrier,et al.  Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. , 1999, The Journal of pharmacology and experimental therapeutics.

[14]  P. Prasit,et al.  Synthesis and biological evaluation of 2,3-diarylthiophenes as selective Cox-2 and Cox-1 inhibitors , 1995 .

[15]  N. Ackerman,et al.  Anti-inflammatory and safety profile of DuP 697, a novel orally effective prostaglandin synthesis inhibitor. , 1990, The Journal of pharmacology and experimental therapeutics.

[16]  C. Koboldt,et al.  Conformationally restricted 1,5-diarylpyrazoles are selective COX-2 inhibitors , 1996 .

[17]  C. Koboldt,et al.  1,2-Diarylpyrroles as potent and selective inhibitors of cyclooxygenase-2. , 1997, Journal of medicinal chemistry.

[18]  D. Bonnet-Delpon,et al.  A SELECTIVE CONVERSION OF SULFIDE TO SULFOXIDE IN HEXAFLUORO-2-PROPANOL , 1998 .

[19]  R. S. Rogers,et al.  Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). , 1997, Journal of medicinal chemistry.

[20]  M. Percival,et al.  The discovery of rofecoxib, [MK 966, Vioxx, 4-(4'-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2-inhibitor. , 1999, Bioorganic & medicinal chemistry letters.

[21]  C. Brideau,et al.  A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors , 1996, Inflammation Research.