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14 results on '"GRANETO, M. J."'

3. ChemInform Abstract: 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)benzenesulfonamide (SC-58635, Celecoxib).

Author

PENNING, T. D., primary, TALLAY, J. J., additional, BERTENSHAW, S. R., additional, CARTER, J. S., additional, COLLINS, P. W., additional, DOCTER, S., additional, GRANETO, M. J., additional, LEE, L. F., additional, MALECHA, J. W., additional, MIYASHIRO, J. M., additional, and ET AL., ET AL., additional

Published
2010
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6. 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]benzenesulfonamide (SC-58635, Celecoxib)

Author

Penning, T. D., Talley, J. J., Bertenshaw, S. R., Carter, J. S., Collins, P. W., Docter, S., Graneto, M. J., Lee, L. F., Malecha, J. W., Miyashiro, J. M., Rogers, R. S., Rogier, D. J., Yu, S. S., Anderson, G. D., Burton, E. G., Cogburn, J. N., Gregory, S. A., Koboldt, C. M., Perkins, W. E., Seibert, K., Veenhuizen, A. W., Zhang, Y. Y., and Isakson, P. C.

Abstract

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure−activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

Published
1997

13. 4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2).

Author

Talley JJ, Bertenshaw SR, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Norman BH, Rogier DJ Jr, Zwwifel BS, and Seibert K

Subjects
Animals, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Humans, Membrane Proteins, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cyclooxygenase Inhibitors pharmacology, Isoenzymes drug effects, Oxazoles pharmacology, Prostaglandin-Endoperoxide Synthases drug effects
Abstract

A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2.

Published
1999
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14. 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).

Author

Penning TD, Talley JJ, Bertenshaw SR, Carter JS, Collins PW, Docter S, Graneto MJ, Lee LF, Malecha JW, Miyashiro JM, Rogers RS, Rogier DJ, Yu SS, AndersonGD, Burton EG, Cogburn JN, Gregory SA, Koboldt CM, Perkins WE, Seibert K, Veenhuizen AW, Zhang YY, and Isakson PC

Subjects
Animals, Arthritis, Experimental drug therapy, Arthritis, Rheumatoid drug therapy, Carrageenan pharmacology, Celecoxib, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors chemistry, Cyclooxygenase Inhibitors pharmacokinetics, Hyperalgesia drug therapy, Magnetic Resonance Spectroscopy, Male, Membrane Proteins, Molecular Structure, Osteoarthritis drug therapy, Pyrazoles, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Structure-Activity Relationship, Cyclooxygenase Inhibitors chemical synthesis, Cyclooxygenase Inhibitors pharmacology, Isoenzymes metabolism, Prostaglandin-Endoperoxide Synthases metabolism, Sulfonamides chemical synthesis, Sulfonamides pharmacology
Abstract

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3-(trifluoromethyl)- H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

Published
1997
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