Heterocyclic Synthesis via Enaminones: Synthesis and Molecular Docking Studies of Some Novel Heterocyclic Compounds Containing Sulfonamide Moiety
Author(s)
Ahmed Abd El-Hameed Hassan
ABSTRACT
4-Acetyl-N, N-diethylbenzenesulfonamide (1) was condensed with dimethylformamide dimethy-lacetal (DMF-DMA) to yield the enaminone, which reacts readily with different reagents to give the corresponding pyrazoles, triazolopyrimidine, imidazopyridine, pyrimidopyrimidine, pyrazolopyrimidine, benzofuran, pyranone, pyridine, pyrimidine and pyrazolopyridazine derivatives. These compounds were designed to comply with the general features of sulfonamide pharmacophore which act as Cyclooxygenase (COX-2) inhibitors. Virtual screening using molecular docking studies of the synthesized compounds was performed by (MOE), the molecular docking results indicate that, some synthesized compounds suitable inhibitor against (COX-2) with further modification.
4-Acetyl-N, N-diethylbenzenesulfonamide (1) was condensed with dimethylformamide dimethy-lacetal (DMF-DMA) to yield the enaminone, which reacts readily with different reagents to give the corresponding pyrazoles, triazolopyrimidine, imidazopyridine, pyrimidopyrimidine, pyrazolopyrimidine, benzofuran, pyranone, pyridine, pyrimidine and pyrazolopyridazine derivatives. These compounds were designed to comply with the general features of sulfonamide pharmacophore which act as Cyclooxygenase (COX-2) inhibitors. Virtual screening using molecular docking studies of the synthesized compounds was performed by (MOE), the molecular docking results indicate that, some synthesized compounds suitable inhibitor against (COX-2) with further modification.
Cite this paper
El-Hameed Hassan, A. (2014) Heterocyclic Synthesis via Enaminones: Synthesis and Molecular Docking Studies of Some Novel Heterocyclic Compounds Containing Sulfonamide Moiety. International Journal of Organic Chemistry, 4, 68-81. doi: 10.4236/ijoc.2014.41009.
El-Hameed Hassan, A. (2014) Heterocyclic Synthesis via Enaminones: Synthesis and Molecular Docking Studies of Some Novel Heterocyclic Compounds Containing Sulfonamide Moiety. International Journal of Organic Chemistry, 4, 68-81. doi: 10.4236/ijoc.2014.41009.
References
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[1] Ferraz, H.M.C. and Goncalo, E.R.S. (2007) Recent Preparations and Synthetic Applications of Enaminones. Química Nova, 30, 957-964.
http://dx.doi.org/10.1590/S0100-40422007000400035 [2] Riyadh, S.M., Abdelhamid, I.A., Al-Matar, H.M., Hilmy, N.M. and Elnagdi, M.H. (2008) Enamines as Precursors to Polyfunctional Heteroaromatic Compounds; a Decade of Development. Heterocycles, 75, 1849-1905.
http://dx.doi.org/10.3987/REV-07-625 [3] Elassar, A.Z.A. and El-Khair, A.A. (2003) Recent Developments in the Chemistry of Enaminones. Tetrahedron, 59, 8463-8480.
http://dx.doi.org/10.1016/S0040-4020(03)01201-8 [4] Stanovnik, B. and Svete, J. (2004) Synthesis of Heterocycles from Alkyl 3-(Dimethylamino)Propenoates and Related Enaminones. Chemical Reviews, 104, 2433-2480.
http://dx.doi.org/10.1021/cr020093y [5] Yermolayev, S.A., Gorobets, N.Y., Lukinova, E.V., Shishkin, O.V., Shishkina, S.V. and Desenko, S.M. (2008) An Efficient Synthesis of N1-Substituted 2,5-Dioxo-1,2,5,6,7,8-Hexahydro 3-Quinolinecarboxamide via Enolate Salts. Tetrahedron, 64, 4649-4655.
http://dx.doi.org/10.1016/j.tet.2008.02.095 [6] Gorobets, N.Y., Yousefi, B.H., Belaj, F. and Kappe, C.O. (2004) Rapid Microwave-Assisted Solution Phase Synthesis of Substituted 2-Pyridone Libraries. Tetrahedron, 60, 8633-8644.
http://dx.doi.org/10.1016/j.tet.2004.05.100 [7] Drews, J. (2000) Drug Discovery: A Historical Perspective. Science, 287, 1960-1964.
http://dx.doi.org/10.1126/science.287.5460.1960 [8] Supuran, C.T., Casini, A. and Scozzafava, A. (2003) Protease Inhibitors of the Sulfonamide Type: Anticancer, Antiinflammatory, and Antiviral Agents. Medicinal Research Reviews, 23, 535.
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http://dx.doi.org/10.1007/s00044-010-9332-3 [11] Boyd 3rd, A.E. (1988) Sulfonylurea Receptors, Ion Channels, and Fruit Flies. Diabetes, 37, 847-850.
http://dx.doi.org/10.2337/diab.37.7.847 [12] Kamel, M.M., Ali, H.I., Anwar, M.M., Mohamed, N.A. and Soliman, A.M. (2010) Synthesis, Antitumor Activity and Molecular Docking Study of Novel Sulfonamide-Schiff’s Bases, Thiazolidinones, Benzothiazinones and Their C-Nucleoside Derivatives. European Journal of Medicinal Chemistry, 45, 572-580.
http://dx.doi.org/10.1016/j.ejmech.2009.10.044 [13] Nair, B. and Taylor-Gjevre, R. (2010) A Review of Topical Diclofenac Use in Musculoskeletal Disease. Pharmaceuticals, 3, 1892-1908.
http://dx.doi.org/10.3390/ph3061892 [14] Gabriel, S.E. and Matteson, E.L. (1995) Economic and Quality-of-Life Impact of NSAIDs in Rheumatoid Arthritis: A Conceptual Framework and Selected Literature Review. Pharmacoeconomics, 8, 479-490.
http://dx.doi.org/10.2165/00019053-199508060-00004 [15] Zochling, J., Bohl-Bühler, M.H.J., Baraliakos, X., Feldtkeller, E. and Braun, J. (2006) Nonsteroidal Anti-Inflammatory Drug Use in Ankylosing Spondylitis—A Population-Based Survey. Clinical Rheumatology, 25, 794-800.
http://dx.doi.org/10.1007/s10067-005-0132-y [16] Hochberg, M.C. (2005) COX-2 Selective Inhibitors in the Treatment of Arthritis: A Rheumatologist Perspective. Current Topics in Medicinal Chemistry, 5, 443-448.
http://dx.doi.org/10.2174/1568026054201695 [17] Warden, J.S. (2010) Prophylactic Use of NSAIDs by Athletes: A Risk/Benefit Assessment. The Physician and Sports Medicine, 38, 132-138.
http://dx.doi.org/10.3810/psm.2010.04.1770 [18] Guyton, C.A. and Hall, J.E. (1998) Textbook of Medical Physiology. 9th Edition, Harcourt Asia Pte. Ltd. [19] Vane, J.R., Bakhle, Y.S. and Bolting, R.M. (1998) Cyclooxygenases 1 and 2. Annual Review of Pharmacology and Toxicology, 38, 97-120.
http://dx.doi.org/10.1146/annurev.pharmtox.38.1.97 [20] Guslandi, M. (1997) Gastric Toxicity of Antiplatelet Therapy with Low-Dose Aspirin. Drugs, 53, 1-5.
http://dx.doi.org/10.2165/00003495-199753010-00001 [21] Mazumdar, K., Dutta, N., Dastidar, S., Motohashi, N. and Shirataki, Y. (2006) Diclofenac in the Management of E. coli Urinary Tract Infections. In Vivo, 20, 613-619. [22] Dutta, N., Annadurai, S., Mazumdar, K., Dastidar, S.G., Kristiansen, J., Molnar, J., Martins, M. and Amaral, L. (2000) The Antibacterial Action of Diclofenac Shown by Inhibition of DNA Synthesis. International Journal of Antimicrobial Agents, 14, 249-251.
http://dx.doi.org/10.1016/S0924-8579(99)00159-4 [23] Sriram, D., Yogeeswari, P. and Devakaram, R. (2006) Synthesis, in Vitro and in Vivo Antimycobacterial Activities of Diclofenac Acid Hydrazones and Amides. Bioorganic & Medicinal Chemistry, 14, 3113-3118.
http://dx.doi.org/10.1016/j.bmc.2005.12.042 [24] Bhandari, S., Bothara, K., Raut, M., Patil, A., Sarkate, A. and Mokale, J. (2008) Design, Synthesis and Evaluation of Anti-Inflammatory, Analgesic and Ulcerogenicity Studies of Novel S-Substituted Phenacyl-1,3,4-Oxadiazole-2-Thiol and Schiff Bases of Diclofenac Acid as Nonulcer-ogenic Derivatives. Bioorganic & Medicinal Chemistry, 16, 1822-1831.
http://dx.doi.org/10.1016/j.bmc.2007.11.014 [25] Amir, M. and Shikha, K. (2004) Synthesis and Anti-Inflammatory, Analgesic, Ulcerogenic and Lipid Peroxidation Activities of Some New 2-[(2, 6-Dichloroanilino) Phenyl]Acetic Acid Derivatives. European Journal of Medicinal Chemistry, 39, 535-545.
http://dx.doi.org/10.1016/j.ejmech.2004.02.008 [26] Barbaric, M., Kralj, M., Marjanovic, M., Husnjak, I., Pavelic, K., Filipovic Grcic, J., Zorc, D. and Zorc, B. (2007) Synthesis and in Vitro Antitumor Effect of Diclofenac and Fenoprofen Thiolated and Nonthiolated Polyaspartamide-Drug Conjugates. European Journal of Medicinal Chemistry, 42, 20-29.
http://dx.doi.org/10.1016/j.ejmech.2006.08.009 [27] Oza, V., Smith, C., Raman, P., Koepf, E., Lashuel, H., Petrassi, H., Chiang, K., Powers, P., Sachettinni, J. and Kelly, J. (2002) Synthesis, Structure, and Activity of Diclofenac Analogues as Transthyretin Amyloid fibril Formation Inhibitors. Journal of Medicinal Chemistry, 45, 321-332.
http://dx.doi.org/10.1021/jm010257n [28] Ramesh, K., Narayana Murthy, S., Karnakar, K. and Nageswar, Y.V.D. (2011) DABCO-Promoted Three-Component Reaction between Amines, Dialkyl Acetylenedicarboxylates, and Glyoxal. Tetrahedron Letters, 52, 3937-3941.
http://dx.doi.org/10.1016/j.tetlet.2011.05.100 [29] Hafiz, I.S. (2000) Enaminonitriles in Heterocyclic Synthesis: Synthesis of New 1, Dihydropyridine Pyrazolo [1, 5-a] Pyrimidine, Aminothiophene and Pyridine Derivatives. Zeitschrift fur Naturforschung, 55, 321. [30] Kiefer, J.R., Pawlitz, J.L., Moreland, K.T., Stegeman, R.A., Hood, W.F., Gierse, J.K., Steven, A.M., Goodwin, D.C., Rowlinson, S.W., Marnett, L.J., Stallings, W.C. and Kurumbail, R.G. (2000) Structural Insights into the Stereochemistry of the Cyclooxygenase Reaction. Nature, 405, 97-101. [31] Eweiss, N.F. and Osman, A. (1980) Synthesis of Heterocycles. Part II. New Routes to Acetylthiadiazolines and Alkyla-zothiazoles. Journal of Heterocyclic Chemistry, 17, 1713-1718.
http://dx.doi.org/10.1002/jhet.5570170814 [32] Nagakura, M., Ota, T., Shimadzu, N., Kawamura, K., Eto, Y. and Wada, Y. (1979) Syntheses and Antiinflammatory Actions of 4,5,6,7-Tetrahydroindazole-5-Carboxylic Acids. Journal of Medical Chemistry, 22, 48-52.
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