QSAR on Heteroaryl-Phenyl-Substituted Pyrazole Derivatives as Selective and Potent Canine COX-2 Inhibitors
Abstract
A series of heteroaryl-phenyl-substituted pyrazole derivatives was subjected to QSAR analysis and the equations generated thereof showed good correlation between COX-2 inhibitory activity and physico-chemical as well as steric properties of the derivatives. One of the significant equations generated has a r value of 0.859 and cross validated r2 (q2) value of 0.534. The contributing parameters include Connolly Accessible Area (CAA), Principal Moment of Inertia at z-axis (PMZ) and Partition Coefficient (PC).
Keywords:
COX-2, QSAR, steric parameters, physicochemical properties, regression, statistical validation
References
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2. Whittle BJR., Higgs GA., Eakins KE., Moncada S, Vane JR. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa; Nature (Lond). 1980; 284: 271–3.
3. Xie W, Robertson DL, Simmons DL. Mitogen-inducible Prostaglandin G/H synthase: A New Target for Nonsteroidal Antiinflammatory Drugs; Drug. Dev. Res. 1992;25: 249-65.
4. Maier JA, Hla T, Maciag T. Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells. J. Biol. Chem. 1990; 265: 10805–8.
5. O’Banion MK, Winn V D, Young DA. cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase; Proc. Natl. Acad. Sci. USA. 1992; 89: 4888–92.
6. DeWitt DL, Smith WL. Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence; Proc. Natl. Acad. Sci. USA. 1988; 85: 1412–6.
7. Smith WL, Garavito RM., DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2; J. Biol. Chem. 1996; 271: 33157-60.
8. Fox SM, Johnston SA.. J. Am. Vet. Med. Assoc. 1997; 210:1493.
9. Li J, DeMello KML, Cheng H., Sakya SM, Bronk BS, Rafka RJ, Jaynes BH, Ziegler CB, Kilroy C, Mann D W, Nimz E L, Lynch MP, Haven ML, Kolosko NL, Minich ML, Li C, Dutra JK, Rast B, Crosson RM, Morton BJ, Kirk GW, Callaghan KM, Koss DA, Shavnya A, Lund LA, Seibel SB, Petras CF, Silvia A. Bioorg. Med. Chem. Lett. 2004; 14:95.
10. Streppa HK, Jones C J, Budsberg SC. Am. J. Vet. Res. 2002; 63:91.
11. Ricketts AP, Lundy KM, Seibel S B. Am. J. Vet. Res. 1998; 59:1441.
12. Millis DL, Weigel JP, Moyers T, Buonomo F. C. Vet. Ther,. 2002; 3: 453.
13. Black WC, Anderson DR, Brideau C, Chauret N, Chern R T, Chen J, Drag M, Fortin R., Hanson P, Haven M, Hickey GJ, McCann ME., Patrick D, Wang ZY, Young RN. Drugs Future. 2002; 27 (Suppl. A): 142.
14. Hengmiao C, Kristin M, DeMello L, Sakya M, Kazuo A, Kawamura K, Kato T, Robert J, Rafka B, Jaynes H, Carl B, Ziegler R, Stevens L, Lund A, Mann DW, Kilroy C, Haven ML, Nimz EL, Dutra JK, Li C, Minich ML, Kolosko NL, Petras C, Silvia AM, Seibela SB. Bioorg. Med. Chem. Lett., 2006;16: 2076-2080.
15. Gupta AK, Babu MA, Kaskhedikar SG. Ind. J. Pharm. Sci. 2004; 66: 396.
16. Schaper KJ. Quant. Struct. Act. Relat. 1999; 18: 354.
17. Wold S, Eriksson L. In QSAR: Chemometric Methods in Molecular Design. Waterbeemd H van de Ed. VCH Weinheim. 1995; 2: 321.
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How to Cite
Agrawal, R., A. Mishra, and S. S. Pancholi. “QSAR on Heteroaryl-Phenyl-Substituted Pyrazole Derivatives As Selective and Potent Canine COX-2 Inhibitors”. Current Research in Pharmaceutical Sciences, Vol. 1, no. 2, Dec. 2011, pp. 68-78, https://crpsonline.com/index.php/crps/article/view/39.
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