Synthesis and structure-activity relationship studies of 1,3-diarylprop-2-yn-1-ones: Dual inhibitors of cyclooxygenases and lipoxygenases

Journal of Medicinal Chemistry

Volumn 49, Issue 5, 2006, Pages 1668-1683

  Rao, P N Praveen ^a   Chen, Qiao Hong ^a   Knaus, Edward E ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 (4 METHANESULFONYLPHENYL) 1 (3 HYDROXY 4 METHOXYPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (3 METHOXYPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (3 NITROPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (3,4 DIFLUOROPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 CYANOPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 FLUOROPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 HYDROXY 3 METHOXYPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 ISOPROPYLPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 METHOXYNAPHTHALEN 1 YL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 METHOXYPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 NITROPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 (4 TRIFLUOROMETHYLPHENYL)PROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 FURAN 3 YLPROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 ISOXAZOL 5 YLPROP 2 YN 1 ONE; 3 (4 METHANESULFONYLPHENYL) 1 NAPHTHALEN 1 YLPROP 2 YN 1 ONE; ACETYLSALICYLIC ACID; ARGININE; BENZOFURAN DERIVATIVE; CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2 INHIBITOR; DIHYDRODIMETHYLBENZOFURAN; HISTIDINE; ISOLEUCINE; LICOFELONE; LIPOXYGENASE INHIBITOR; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN SYNTHASE INHIBITOR; ROFECOXIB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BINDING SITE; CATALYSIS; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROGEN BOND; HYDROPHOBICITY; IC 50; MOLECULAR MODEL; NONHUMAN; PAW EDEMA; PHARMACOPHORE; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ALKYNES; ANALGESICS; ANIMALS; ARACHIDONATE 15-LIPOXYGENASE; ARACHIDONATE 5-LIPOXYGENASE; CARRAGEENAN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; CYCLOOXYGENASE INHIBITORS; EDEMA; LIPOXYGENASE INHIBITORS; MICE; MODELS, MOLECULAR; PAIN MEASUREMENT; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33644868745     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0510474     Document Type: Article

References (29)

1. 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.; Isakson, P. C. 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). J. Med. Chem. 1997, 40, 1347-1365.
2. De Leval, X.; Julemont, F.; Benoit, V.; Frederich, M.; Pirotte, B.; Dogne, J. M. First and second generations of COX-2 selective inhibitors. Mini Rev. Med. Chem. 2004, 4, 597-601.
3. Dogné, J. M.; Supuran, C. T.; Pratico, D. Adverse cardiovascular effects of the coxibs. J. Med. Chem. 2005, 48, 2251-2257.
4. Solomon D. H.; Selective cyclooxygenase-2 inhibitors and cardiovascular events. Arthritis Rheum. 2005 52, 1968-1978.
5. Vane, J. R.; Botting, R. M. Antiinflammatory drugs and their mechanism of action. Inflamm Res. 1998, 47, S78-S87.
6. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoids biology, Science 2001. 294, 1875-1890.
7. Drazen, J. M.; Israel, E.; O'Byrne, P. M. Treatment of asthma with drugs modifying the leukotriene pathway. N. Engl. J. Med. 1999, 340, 197-206.
8. Zhao, L.; Funk, C. D. Lipoxygenase pathways in atherogenesis. Trends Cardiovasc. Med. 2004, 14, 191-195.
9. Julemont, F.; Dogne, J. M.; Pirotte, B.; de Leval, X. Recent development in the field of dual COX/5-LOX inhibitors. Mini Rev. Med. Chem. 2004, 4, 633-638.
10. Charlier, C.; Michaux, C. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur. J. Med. Chem. 2003, 38, 645-659.
11. Janusz J. M.; Young P. A.; Ridgeway, J. M.; Scherz, M. W.; Enzweiler, K.; Wu, Li.; Gan, L.; Darolia, R.; Matthews, R. S.; Hennes, D.; Kellstein, D. E.; Green, S. A.; Tulich, J. L.; Rosario-Jansen, T.; Magrisso, I. J.; Wehmeyer, K. R.; Kuhlenbeck, D. L.; Eichhold, T. H.; Dobson, R. L.; Sirko, S. P.; Farmer, R. W. New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-butyl-2,3-dihydro- 3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent. J. Med. Chem. 1998, 41, 1112-1123.
12. Alvaro-Gracia, J. M. Licofelone-clinical update on a novel LOX/ COX inhibitor for the treatment of osteoarthritis. Rheumatology 2004, 43, i21-i25.
13. Pommery, N.; Taverne, T.; Telliez, A.; Goossens, L.; Charlier, C.; Pommery, J.; Goossens, J. F.; Houssin, R.; Durant, F.; Henichart, J. P. New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy. J. Med. Chem. 2004, 47, 6195-6206.
14. Ye, Y. N.; Wu, W. K.; Shin, V. Y.; Bruce, I. C.; Wong, B. C.; Cho, C. H. Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogensis 2005, 26, 827-834.
15. Jahng, Y.; Zhao, L. X.; Moon, Y. S.; Basnet, A.; Kim, E. K.; Chang, H. W.; Ju, H. K.; Jeong, T. C.; Lee, E. S. Simple aromatic compounds containing propenone moiety show considerable dual COX/5-LOX inhibitory activities. Bioorg. Med. Chem. Lett. 2004, 14, 2559-2562.
16. Rao, P. N. P.; Chen, Q. H.; Knaus, E. E. Synthesis and biological evaluation of 1,3-diphenylprop-2-yn-1-ones as dual inhibitors of cyclooxygenases and lipoxygenases. Bioorg. Med. Chem. Lett. 2005, 15, 4842-4845.
17. Gavrilov, L. D.; Meshcheryakov, V. I.; Glazunova, N. P.; Kalyagina, G. F.; Dobronravova, Z. A.; Vereschchagin, L. I. Synthesis of diarylpropynones and their antibiotic activity. Pharm. Chem. J. 1978, 12, 1146-1149.
18. Ahmed, M. S. M.; Mori, A. Carbonylative Sonogashira coupling of terminal alkynes with aqueous ammonia. Org. Lett. 2003, 5, 3057-3060.
19. Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Kawamura, T.; Uemura, S. Oxovanadium complex-catalyzed aerobic oxidation of propargylic alcohols. J. Org. Chem. 2002, 67, 6718-6724.
20. Rao, P. N. P.; Uddin, M. J.; Knaus, E. E. Design, synthesis, and structure-activity relationship studies of 3,4,6-triphenylpyran-2-ones as selective cyclooxygenase-2 inhibitors. J. Med. Chem. 2004, 47, 3972-3990.
21. Weiss, K. L.; Alshafie, G.; Chapman, J. S.; Mershon, S. M.; Abou-Isaa, H.; Clagett-Dame, M.; Curley, R. W. An unhydrolyzable analogue of N-(4-hydroxyphenyl)retinamide, synthesis and preliminary biological studies. Bioorg. Med. Chem. Lett. 2001, 11, 1583-1586.
22. Jiang, Z. Y.; Wang, Y. G. A Mild, Efficient and selective cleavage of aryl tert-butyldimethysilyl ethers using KOH in ethanol. Chem. Lett. 2003, 32, 568-569.
23. Cox, R. J.; Ritson, D. J.; Dane, T. A.; Berge, J.; Charmant, J. P. H.; Kantacha, A. Room temperature palladium catalyzed coupling of acyl chlorides with terminal alkynes. Chem. Commun. 2005, 1037-1039.
24. Luong, C.; Miller, A.; Barnett, J.; Chow, J.; Ramesha, C.; Browner, M. F. Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2. Nature Struct. Biol. 1996, 3, 927-933.
25. Gillmor, S. A.; Villasenor, A.; Fletterick, R.; Sigal, E.; Browner, M. F. The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of tsubstrate specificity. Nature Struct. Biol. 1997, 4, 1003-1009.
26. Prasit, P.; Wang, Z.; Brideau, C.; Chan, C. C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J. F.; Ford-Hutchinson, A. W.; Gauthier, J. Y.; Gordon, R.; Guay, J.; Gresser, M.; Kargman, S.; Kennedy, B.; Leblanc, Y.; Leger, S.; Mancini, J.; O'Neill, G. P.; Ouellet, M.; Percival, M. D.; Perrier, H.; Riendeau, D.; Rodger, I.; Zamboni, R.; Boyce, S.; Rupniak, N.; Forrest, M.; Visco, D.; Patrick, D. The discovery of rofecoxib, [MK 966, VIOXX, 4-(4′-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2 inhibitor. Bioorg. Med. Chem. Lett. 1999, 9, 1773-1778.
27. Winter, C. A.; Risley, E. A.; Nuss, G. W.: Carrageenan-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc. Soc. Exp. Biol. Med. 1962, 111, 544-552.
28. Kumar, P.; Knaus, E. E. Synthesis and antiinflammatory activity of N-substituted dihydropyridylacetic acids, esters and amides. Drug Des. Delivery 1987, 2, 145-149.
29. Fukawa, K.; Kawano, O.; Hibi, M.; Misaka, N.; Ohba, S.; Hatanaka, Y. Method for evaluating analgesic agents in rats. J. Pharmacol. Methods 1980, 4, 251-259.