IJOC  Vol.4 No.1 , March 2014
Heterocyclic Synthesis via Enaminones: Synthesis and Molecular Docking Studies of Some Novel Heterocyclic Compounds Containing Sulfonamide Moiety
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.

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.
References
[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.
http://dx.doi.org/10.1002/med.10047

[9]   Supuran, C.T. and Scozzafava, A. (2000) Carbonic Anhydrase Inhibitors and Their Therapeutic Potential. Expert Opinion on Therapeutic Patents, 10, 575-600.

[10]   Ghorab, M.M., Ragab, F.A., Heiba, H.I., Arafa, R.K. and El-Hossary, E.M. (2011) Docking Study, in Vitro Anticancer Screening and Radiosensitizing Evaluation of Some New Fluorine-Containing Quinoline and Pyrimidoquinoline Derivatives Bearing a Sulfonamide Moiety. Medicinal Chemistry Research, 20, 388-400.
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.
http://dx.doi.org/10.1021/jm00187a012

[33]   Shawali, A.S. and Abdelhamide, A.O. (1976) Reaction of Dimethylphenacylsulfonium Bromide with N-Nitrosoacetarylamides and Reactions of the Products with Nucleophiles. Bulletin of the Chemical Society of Japan, 49, 321-324.
http://dx.doi.org/10.1246/bcsj.49.321

[34]   Al-Zaydi, K.M. (2003) Microwave Assisted Synthesis, Part 1: Rapid Solventless Synthesis of 3-Substituted Coumarins and Benzocoumarins by Microwave Irradiation of the Corresponding Enaminones. Molecules, 8, 541-555.
http://dx.doi.org/10.3390/80700541

[35]   Biere, H., Böttcher, I. and Kapp, J. (1983) Nonsteroidal Anti-Inflammatory Agents. 11. Antiphlogistic Pyrazole Derivatives, III. Archiv der Pharmazie (Weinheim), 316, 608-616.

[36]   El-Taweel, F.M. and Elnagdi, M.H. (2001) Studies with Enaminones: Synthesis of New Coumarin-3-yl Azoles, Coumarin-3-yl Azines, Coumarin-3-yl Azoloazines, Coumarin-3-yl Pyrone and Coumarin-2-yl Benzo[b]Furans. Journal of Heterocyclic Chemistry, 38, 981-984.
http://dx.doi.org/10.1002/jhet.5570380428

[37]   Hochgesang, G.P. and Marnett, L.J. (2000) Tyrosine-385 Is Critical for Acetylation of Cyclooxygenase-2 by Aspirin. Journal of the American Chemical Society, 122, 6514-6515.
http://dx.doi.org/10.1021/ja0003932

[38]   Rowlinson, S.W., Kiefer, J.R., Prusakiewcz, J.J., Pawlitz, J.L., Kozak, K.R., Kalgutkar, A.S., Stallings, W.C., Kurumbail, R.G. and Marnett, L. (2003) A Novel Mechanism of Cyclooxygenase-2 Inhibition Involving Interactions with Ser-530 and Tyr-385. Journal of Biological Chemistry, 278, 45763-45769.
http://dx.doi.org/10.1074/jbc.M305481200

[39]   Kurumbail, R.G., Stevens, A.M., Gierse, J.K., McDonald, J.J., Stegeman, R.A., Pak, J.Y., Gildehaus, D., Miyashiro, J.M., Penning, T.D., Seibert, K., Isakson, P.C. and Stallings, W.C. (1996) Structural Basis for Selective Inhibition of Cyclooxygenase-2 by Anti-Inflammatory Agents. Nature, 384, 644-648.
http://dx.doi.org/10.1038/384644a0

[40]   Sidhu, R.S., Lee, J.Y., Yuan, C. and Smith, W.L. (2010) Comparison of Cyclooxygenase-1 Crystal Structures: Cross-Talk between Monomers Comprising Cyclooxygenase-1 Homodimers. Biochemistry, 49, 7069-7079.
http://dx.doi.org/10.1021/bi1003298

[41]   Chemical Computing Group. Inc., MOE, 2009, 10.

[42]   Halgren, T.A. (1996) Merck Molecular Force Field I. Basis, Form, Scope, Parameterization, and Performance of MMFF94. Journal of Computational Chemistry, 17, 490-519.
http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P

[43]   Clark, D.E. and Pickett, S.D. (2000) Computational Methods for the Prediction of ‘Drug-Likeness’. Drug Discovery Today, 5, 49-58.
http://dx.doi.org/10.1016/S1359-6446(99)01451-8

[44]   Wildman, S.A. and Crippen, G.M. (1999) Prediction of Physicochemical Parameters by Atomic Contribution. Journal of Chemical Information and Computer Sciences, 39, 868-873.
http://dx.doi.org/10.1021/ci990307l

[45]   Fukui, K. (1982) Role of Frontier Orbitals in Chemical Reactions. Science, 218, 747-754.
http://dx.doi.org/10.1126/science.218.4574.747

[46]   Jose, A.P. and Robert, R.S. (1991) Carbene/Anion Complexes. Unusual Structural and Thermochemical Features of .Alpha.-Halocarbanions in the Gas Phase. Journal of the American Chemical Society, 113, 1845-1847.

[47]   Parr, R.G., Szentpaly, L.V. and Liu, S. (1999) Electrophilicity Index. Journal of the American Chemical Society, 121, 1922-1924.
http://dx.doi.org/10.1021/ja983494x

[48]   Chattaraj, P.K., Maiti, B. and Sarkar, U. (2003) Philicity: A Unified Treatment of Chemical Reactivity and Selectivity. The Journal of Physical Chemistry A, 107, 4973-4975.
http://dx.doi.org/10.1021/jp034707u

[49]   Parr, R.G., Donnelly, R.A., Levy, M. and Palke, W.E. (1978) Electronegativity: The Density Functional Viewpoint. The Journal of Chemical Physics, 68, 3801-3814.
http://dx.doi.org/10.1063/1.436185

[50]   Parr, R.G. and Pearson, R.G. (1983) Absolute Hardness: Companion Parameter to Absolute Electronegativity. Journal of the American Chemical Society, 105, 7512-7516.
http://dx.doi.org/10.1021/ja00364a005

[51]   Parr, R.G. and Yang, W. (1989) Density Functional Theory of Atoms and Molecules. Oxford University Press, Oxford.

 
 
Top