IJOC  Vol.3 No.2 , June 2013
Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-d]pyrimidines
ABSTRACT

During the last few years, condensed thienopyrimidine derivatives have received considerable attention. The therapeutic importance of thienopyrimidines prompted us to synthesize some of spiro(benzothieno[2,3-d]pyrimidine-4-one) derivatives. Some of the novel benzothino-pyrimidine derivatives 3a, 9b, 10b, 11a, 11b, and 11c showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as reference drugs.


Cite this paper
H. Hafez, O. Al-Duaij and A. El-Gazzar, "Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-d]pyrimidines," International Journal of Organic Chemistry, Vol. 3 No. 2, 2013, pp. 110-118. doi: 10.4236/ijoc.2013.32012.
References
[1]   A. J. Folkes, K. Ahmadi, W. K. Alderton, S. Alix, S. J. Baker, G. Box, I. S. Chuckowree, P. A. Clarke, P. Depledge, S. A. Eccles, L. S. Friedman, A. Hayes, T. C. Hancox, A. Kugendradas, L. Lensun, P. Moore, A. G. Olivero, J. Pang, S. Patel, G. H. Pergl-Wilson, F. I. Raynaud, A. Robson, N. Saghir, L. Salphati, S. Sohal, M. H. Ultsch, M. Valenti, H. J. A. Wall-weber, N. C. Wan, C. Wiesmann, P. Workman, A. Zhyvoloup, M. J. Zvelebil and S. J. Shuttleworth, “The Identification of 2-(1H-Indazol-4-yl)-6-(4methanesulfonylpiperazin-1-yl-methyl)-4-morpholin-4yl-thie-no[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer,” Journal Medicinal Chemistry, Vol. 51, No. 18, 2008, pp. 5522-5532.

[2]   L. D. Jennings, S. L. Kincaid, Y. D. Wang, G. Krishnamurthy, C. F. Beyer, J. P. McGinnis, M. Miranda, C. M. Discafani and S. K. Rabindran, “Parallel Synthesis and Biological Evaluation of 5,6,7,8-Tetrahydrobenzothieno [2,3-d]pyrimidin-4(3H)-one Cytotoxic Agents Selective for p21-Deficient Cells,” Bioorganic & Medicinal Chemistry Letter, Vol. 15, No. 21, 2005, pp. 4731-4735.

[3]   Y. D. Wang, S. Johnson, D. Powell, J. P. McGinnis, M. Miranda and S. K. Rabindran, “Inhibition of Tumor Cell Proliferation by Thieno[2,3-d]pyrimidin-4(1H)-one-based Analogs,” Bioorganic & Medicinal Chemistry Letter, Vol. 15, No. 16, 2005, pp. 3763-3766.

[4]   T. Horiuchi, J. Chiba, K. Uoto and T. Soga, “Discovery of Novel Thieno[2,3-d]pyrimidin-4-yl Hydra-zone-Based Inhibitors of Cyclin D1-CDK4: Synthesis, Biological Evaluation, and Structure-Activity Relationships,” Bioorganic & Medicinal Chemistry Letter, Vol. 19, No. 2, 2009, pp. 305-308.

[5]   A. Angell, C. McGuigan, L. G. Sevillano, R. Snoeck, G. Andrei, E. De Clercq and J. Balzarini “Bicyclic AntiVZV Nucleosides,” Bioorganic & Medicinal Chemistry Letter, Vol. 14, No. 10, 2004, pp. 2397-2399. doi:10.1016/j.bmcl.2004.03.029

[6]   A. Brancale, C. Mcguigan, B. Algain, S. Pascal, R. Benhida, J. L. Fourrey, G. Andrei, R. Snoeck, E. De Clercq and J. Balzarini, “Bicyclic Anti-VZV Nucleosides: Thieno Analogues Retain Full Antiviral Activity,” Bioorganic & Medicinal Chemistry Letter, Vol. 11, No. 18, 2001, pp. 2507-2510.

[7]   M. H. Bhuiyan. K. M. Rahman, K. Hossain, A. Rahim, I. Hossain and M. Abu Naser, “Synthesis and Antimicrobial Evaluation of Some New Thienopyrimidine Derivatives,” Acta pharmaceutica, Vol. 56, No. 4, 2006, pp. 441-450.

[8]   R. V. Chambhare, B. G. Khadse, A. S. Bobde and R. H. Bahekar, “Synthesis and Preliminary Evaluation of Some N-[5-(2-Furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]carboxamide and 3-Substituted-5-(2-furanyl)-2methyl-3H-thieno[2,3-d]pyrimidin-4-ones as Antimicrobial Agents,” European Journal of Me-dicinal Chemistry, Vol. 38, No. 1, 2003, pp. 89-100.

[9]   S. Yousieff and B. E. Bayoumy, “1,3,4-Thiadiazolylthieno Pyrimidines and 1,3,4-Oxadiazolyl Thienopyrimidines for Anti-bacterial Activity,” Journal of Pharmaceutical Sciences, Vol. 31, No. 1-3, 1990, p. 67.

[10]   V. Alagarsamy, S. Vijayakumar and V. R. Solomon, “Synthesis of 2-Mercapto-3-substituted-5,6-dimethylthieno[2,3-d]Pyrimidin-4(3H)-ones as New Analgesic, AntiInflammatory Agents,” Biomed Pharmacother, Vol. 61, No. 5, 2007, pp. 285-291. doi:10.1016/j.biopha.2007.02.008

[11]   V. Alagarsamy, S. Meena, K. V. Ramseshu, V. R. Solomon, K. Thirumurugan, K. Dhanabal and M. Murugan, “Synthesis, Analgesic, Anti-Inflammatory, Ulcerogenic Index and Antibacterial Activities of Novel 2-Methylthio3-substituted-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-ones,” European Journal of Medicinal Chemistry, Vol. 41, No. 11, 2006, pp. 1293-1300.

[12]   I. O. Donkor, L. I. Hui and S. F. Queener, “Synthesis and DHFR Inhibitory Activity of a Series of 6-Substituted2,4-diaminothieno[2,3-d]pyrimidines,” European Journal of Medicinal Chemistry, Vol. 38, No. 6, 2003, pp. 605611.

[13]   H. N. Hafez and A. B. A. El-Gazzar, “Design and Synthesis of 3-Pyrazolyl-thiophene, Thieno[2,3-d]pyrimidines as New Bioactive and Pharmacolog-ical Activities,” Bioorganic & Medicinal Chemistry Letter, Vol. 18, No. 19, 2008, pp. 5222-5227.

[14]   A. B. A. El-Gazzar, H. A. R. Hossein and H. N. Hafez, “Synthesis and Biological Evaluation of Thieno[2,3d]pyrimidine Derivatives as Anti-inflammatory, Analgesic and Ulcerogenic Activity,” Acta Pharmaceutica, Vol. 57, No. 4, 2007, pp. 395-411. doi:10.2478/v10007-007-0032-6

[15]   M. Santagati, M. Modica, A. Santagati, F. Russo and S. Spampinato, “Synthesis of Aminothienopyrimidine and Thienotriazolopyrimidine Derivatives as Potential Anticonvulsant Agents,” Die Pharmazie, Vol. 51, No. 1, 1996, pp. 7-11.

[16]   M. R. Prasad, R. A. Raghuram, R. P. Shanthan, R. K. Subramanian, S. Meena and K. Madhavi, “Synthesis and Adenosine Receptor Binding Studies of Some Novel Triazolothienopyrimidines,” European Journal of Medicinal Chemistry, Vol. 43, No. 3, 2008, pp. 614-620.

[17]   L. P. Melissal, C. G. Wayne, E. Tara, A. N. Jason, L. Patricia, C. J. José, D. Fernando and J. T. Robert, “Design of Novel N-(2,4-Dioxo-1,2,3,4-tetrahydro-thieno[3,2-d] pyrimidin-7-yl)-guanidines as Thymidine Phosphorylase Inhibitors, and Flexible Docking to a Homology Model,” Bioorganic & Medicinal Chemistry Letter, Vol. 13, No. 1, 2003, pp. 107-110.

[18]   H. N. Hafez, H. A. Hussein and A. B. A. El-Gazzar, “Synthesis of Substituted Thieno[2,3-d]pyrimidine-2,4dithiones and Their S-Glycoside Analogues as Potential Antiviral and Antibacterial Agents,” European Journal of Medicinal Chemistry, Vol. 45, No. 9, 2010, pp. 40264034.

[19]   C. J. Shishoo, V. S. Shirsath, I. S. Rathod, M. J. Patil and S. S. Bhargava, “Design Synthesis and Antihistaminic (H1) Activity of Some Condensed 2-(Substituted)arylaminoethylpyrimidine-4-(3H)-ones,” Arzneim Forsch, Vol. 51, No. 3, 2001, pp. 221-231.

[20]   G. A. Winter, E. A. Rislfy and G. W. Nuss, “Carrageenininduced Edema in Hind Paw of Rat as an Assay for Antiinflammatory Drugs,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 111, 1962, pp. 544-547.

[21]   P. Armitage, “Statistical Methods in Medical Research,” 1st Edition, Blackwell Scientific Publ., Oxford, London, 1971.

[22]   G. Woolfe and A. D. MacDonald, “The Evaluation of the Analgesic Action of Pethidine Hydrochloride,” Journal of Pharmacoogy and Experimental Therapeutics, Vol. 80, No. 3, 1944, pp. 300-307.

[23]   A. E. Amr and M. M. Abdulla, “Synthesis and Antiinflammatory Activities of New Cyanopyrane Derivatives Fused with Steroidal Nuclei,” Archiv der Pharmazie Chemistry Life Science, Vol. 339, No. 2, 2006. pp. 88-95. doi:10.1002/ardp.200500209

[24]   M. G. Obukowics, D. J. Walseh, W. J. Salsgiver, C. L. Martin-Berger, K. S. Chinn, K. L. Duffin, A. Ras and P. Needleman, “Novel, Selective Δ6 or Δ5 Fatty Acid Desaturase Inhibitors as Antiinflammatory Agents in Mice,” Journal of Pharmacoogy and Experimental Therapeutics, Vol. 287, No. 1, 1998, pp. 157-166.

[25]   L. Meng, R. Mohan, B. H. B. Kwok, M. Elofssof, N. Sin and C. M. Crews, “Epoxomicin, a Potent and Selective Proteasome Inhibitor, Exhibits in Vivo Antiinflammatory Activity,” Proceedings of the National Academy of Science, USA, Vol. 96, No. 18, 1999, pp. 10403-10408.

[26]   M. Eaton, “Common Animal Models for Spasticity and Pain,” Journal of Rehabilitation Research and Development, Vol. 40, No. 4, 2003, pp. 41-54. doi:10.1682/JRRD.2003.08.0041

 
 
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