Synthesis of 6-(4-methanesulphonamidophenyl)-substituted dihydropyridazinone/ phthalazinone derivatives as potent anti-inflammatory and analgesic agents

Main Article Content

Deepika Sharma Dinesh Kumar Ranju Bansal

Abstract

New 6-(4-methanesulphonamidophenyl)-substituted dihydropyridazinones and their phthalazinone analogues have been synthesized and evaluated for anti-inflammatory and analgesic activities using carrageenan induced paw edema and acetic acid induced writhing models, respectively. Most of the newly synthesized compounds displayed potent anti-inflammatory activity without ulcerogenic side effects. Both pyridazinone as well as phthalazinone analogues displayed moderate analgesic activity at 40 mg/kg. In general, all pyridazinone derivatives showed activity better than their phthalazinone counterparts.

Article Details

How to Cite
SHARMA, Deepika; KUMAR, Dinesh; BANSAL, Ranju. Synthesis of 6-(4-methanesulphonamidophenyl)-substituted dihydropyridazinone/ phthalazinone derivatives as potent anti-inflammatory and analgesic agents. Medical Research Archives, [S.l.], n. 1, dec. 2014. ISSN 2375-1924. Available at: <http://journals.ke-i.org/index.php/mra/article/view/13>. Date accessed: 19 sep. 2017. doi: https://doi.org/10.18103/mra.v0i1.13.
Keywords
3(2H)-pyridazinones, phthalazinones, analgesics, anti-inflammatory 3(2H)-pyridazinones, phthalazinones, analgesics,anti-inflammatory agents, ulcerogenic effect
Section
Research Articles

References

Abouzid, K.; Bekhit, S. “Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity.” Bioorg Med Chem 16: (2008) 5547-56.

Asif, M.; Singh, A. “Exploring potential, synthetic methods and general chemistry of pyridazine and pyridazinone: a brief introduction.” Int J Chem Tech Res 2(2) (2010): 1112-28.

Bansal, R.; Thota, S. “Pyridazin-3(2H)-ones: the versatile pharmacophore of medicinal significance.” Med Chem Res 22 (2013): 2539-52.

Chan, C. C.; Boyce, S.; Brideau, C.; Ford-Hutchinson, A. W.; Gordon, R.; Guay, D.; Hill, R. G.; Li, C. S.; Mancini, J.; Penneton, M. “Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach.” J Pharmacol Exp Therap 274 (1995): 1531-37.

Dannhardt, G.; Kiefer, W. “Cyclooxygenase inhibitors--current status and future prospects.” Eur J Med Chem 36 (2001): 109-26.

Dogruer, D. S.; Kupeli, E.; Yeşilada, E.; Sahin, M. F. “Synthesis of new 2-[1(2H)-phthalazinon-2-yl]acetamide and 3-[1(2H)-phthalazinon-2-yl]propanamide derivatives as antinociceptive and anti-inflammatory agents.” Arch Pharm Pharm Med Chem 337 (2004): 303-10.

Dogruer, D. S.; Sahin, M. F.; Küpeli, E.; Yeşilada, E. “Synthesis and analgesic and anti-inflammatory activity of new pyridazinones.” Turk J Chem 27 (2003): 727-38.

Garcia-Nieto, R.; Perez, C.; Checa, A.; Gago, F. “Molecular model of the interaction between nimesulide and human cyclooxygenase-2.” Rheumatology 38 (1999): 14-18.

Kagayama, K.; Morimoto, T.; Nagata, S.; Katoh, F.; Zhang, X.; Inoue, N.; Hashino, A.; Kageyama, K.; Shikaura, J.; Niwa, T. “Synthesis and biological evaluation of novel phthalazinone derivatives as topically active phosphodiesterase 4 inhibitors.” Bioorg Med Chem 17 (2009): 6959-70.

Khaled, A. M. A.; Nadia, A. K.; Eman, M. A.; Hekmat, A. A.; Moustafa, E. E. “Structure-based molecular design, synthesis, and in vivo anti-inflammatory activity of pyridazinone derivatives as nonclassic COX-2 inhibitors.” Med Chem Res 19 (2010): 629-42.

Kumar, D.; Carron, R.; Calle, C. D. L.; Jindal, D. P.; Bansal, R. “Synthesis and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)-ones as potent inodilators.” Acta Pharm 58 (2008): 393-405.

Margaretha, V. M.; Armin, H.; Ivonne, J. V. L.; Geert, J. S.; Ulric, T.; Hendrik, T. Novel selective PDE4 inhibitors. “1. Synthesis, structure-activity relationships, and molecular modeling of 4-(3,4-dimethoxyphenyl)-2H-phthalazin-1-ones and analogues.” J Med Chem 44 (2001): 2511-22.

Nakamura, K.; Tsuji, K.; Konishi, N.; Okumura, H.; Matsuo, M. “Studies on antiinflammatory agents. II. Synthesis and pharmacological properties of 2'-(phenylthio)methanesulfonanilides and related derivatives.” Chem Pharm Bull 41 (1993): 894-906.

Sato, M.; Ishizuka, Y.; Yamaguchi, A. “Pharmacological investigations of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M 73101), a new analgesic and anti-inflammatory drug.” Arzneim.-Forsch Drug Res 31 (1981): 1738-45.

Sato, M.; Yamaguchi, A. “Pharmacological investigations of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M 73101), a new analgesic and anti-inflammatory drug.” Arzneim Forsch 32 (1982): 379-82.

Sircar, I.; Weishaar, R. E.; Kobylarz, D.; Moos, W. H.; Bristol, J. A. “Cardiotonic agents. 7. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from guinea pig cardiac muscle by 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds. Structure-activity relationships and correlation with in vivo positive inotropic activity.” J Med Chem 30 (1987): 1955-62.

Umide, D. O.; Yusuf, O.; Ozgur, D. C. “Synthesis and analgesic effects of 2-(2-carboxyphenylsulfanyl)-N-(4-substitutedphenyl) acetamide derivatives.” Med Chem Res 20 (2011): 152-57.

Vane, J. R. “The fight against rheumatism: from willow bark to COX-1 sparing drugs.” J Physiol Pharmacol 51 (2000): 573-86.

Vane, J. R. “Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.” Nature (New Biology) 231 (1971): 232-35.

Whittle, B. J. R.; Boughton-Smith, N. K.; Moncada, S.; Vane, J. R. “Actions of prostacyclin (PGI2) and its product, 6-oxo-PGF1α on the rat gastric mucosa in vivo and in vitro.” Prostaglandins 15 (1978): 955-68.

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