2,3-Diarylbenzopyran derivatives as a novel class of selective cyclooxygenase-2 inhibitors.

A new series of cyclooxygenase-2(COX-2) inhibitors with naturally occurring flavone as the main skeleton has been synthesized and their biological activities were evaluated for cyclooxygenase inhibitory activity. Rational structural modifications were applied to potent COX-2 inhibitors to obtain the desired pharmacokinetic profiles for improved oral anti-inflammatory activity.

[1]  C. Koboldt,et al.  N-[[(5-methyl-3-phenylisoxazol-4-yl)-phenyl]sulfonyl]propanamide, sodium salt, parecoxib sodium: A potent and selective inhibitor of COX-2 for parenteral administration. , 2000, Journal of medicinal chemistry.

[2]  G. Smith,et al.  Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. , 1972, The Biochemical journal.

[3]  C. Koboldt,et al.  1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active antiinflammatory agents. , 1997, Journal of medicinal chemistry.

[4]  N. Miyaura,et al.  Novel synthesis of isoflavones by the palladium-catalyzed cross-coupling reaction of 3-bromochromones with arylboronic acids or its esters. , 1988 .

[5]  S. Higuchi,et al.  NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions. , 1993, General pharmacology.

[6]  D. Dewitt,et al.  Cox-2-selective inhibitors: the new super aspirins. , 1999, Molecular pharmacology.

[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]  R. Erikson,et al.  Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Norio Miyaura,et al.  The Palladium-Catalyzed Cross-Coupling Reaction of Phenylboronic Acid with Haloarenes in the Presence of Bases , 1982 .

[10]  C. Thiemermann,et al.  Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Bishop,et al.  A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs , 1998, Inflammation Research.

[12]  Hiromasa Hashimoto,et al.  4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1). , 2002, Journal of medicinal chemistry.

[13]  2,2-Dimethyl-4,5-diaryl-3(2H)furanone derivatives as selective cyclo-oxygenase-2 inhibitors. , 2001, Bioorganic & medicinal chemistry letters.

[14]  K. Seibert,et al.  The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. , 1990, The Journal of biological chemistry.