Abstract
A series of some new benzoxazines derivatives have been synthesized using conventional method and solvent-free microwave thermolysis. It was observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of benzoxazines when compared with conventional reaction in a solution phase. All the compounds synthesized were tested for anti-inflammatory activity. Compound 3f, 3h, and 3l showed 74.87, 70.39, and 71.89% of inhibition in rat paw edema, 57.38, 54.27, and 55.47% of protection against acetic acid induced writhings, and 0.08, 0.17, and 0.17 of severity index (SI), respectively compared to 82.33, 63.06, and 1.0 values of ibuprofen. The study showed that these compounds are good and safe anti-inflammatory agents and can be used to develop potent and safe anti-inflammatory agents.
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Akhter M, Husain A, Azad B, Ajmal M (2009) Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles: synthesis and their anti-inflammatory and analgesic activity. Eur J Med Chem 44(6):2372–2378
Beach M, Frechette R (1997) WO Patent Appl 9728167
Chiaradia LD, Mascarello A, Purificação M, Vernal J, Cordeiro MNS, Zenteno ME, Villarino A, Nunes RJ, Yunes RA, Terenzi H (2008) Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Bioorg Med Chem Lett 18:6227–6230
Cioli V, Putzolu S, Rossi V, Sorza Barcellona P, Corradino C (1979) The role of direct tissue contact in the production of gastro-intestinal ulcers by anti-inflammatory drugs in rats. Toxicol Appl Pharmacol 50:283–289
Domínguez JN, León C, Rodrigues J, Gamboa DN, Gut J, Rosenthal PJ (2005) Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J Med Chem 48:3654–3658
Go ML, Wu X, Liu XL (2005) Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 12:483–499
Gokhan N, Erdogan H, Durlu NT, Demirdamar R (1999) Analgesic activity of acylated 2-benzoxazolinone derivatives. Farmaco 54:112–115
Hasan SM, Alam MM, Husain A, Khanna S, Akhtar M, Zaman MS (2009) Synthesis of 6-aminomethyl derivatives of benzopyran-4-one with dual biological properties: anti-inflammatory-analgesic and antimicrobial. Eur J Med Chem 44(12):4896–4903
Herencia F, Ferrandiz ML, Ubeda A, Domiguez JN, Charris JE, Lobo GM, Alcaraz MJ (1998) Synthesis and anti-inflammatory activity of chalcone derivatives. Bioorg Med Chem 8:1169–1174
Ilas J, Anderluh PS, Dolenc MS, Kikelj D (2005) Recent advances in the synthesis of 2H-1,4-benzoxazin-3-(4H)-ones and 3,4-dihydro-2H-1,4-benzoxazines. Tetrahedron 61:7325–7348
Kamei K, Maeda N, Nomura K, Shibata M, Katsuragi-Ogino R, Koyama M, Nakajima M, Inoue T, Ohno T, Tatsuoka T (2006) Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: discovery of Piclozotan. Bioorg Med Chem 14:1978–1992
Khalaj A, Abdollahi M, Kebriaeezadeh A, Adibpour N, Pandi Z, Rasoulamini S (2002) The antinociceptive and antiinflammatory activities and lack of ulcerogenicity of a benzodioxin-4-one and its analog benzoxazine as cyclic acetal-like derivatives of salicylic acid and salicylamide in mice and rats. Ind J Pharmacol 34:184–188
Larsen M, Kromannn H, Kharazmi A, Nielsen SF (2005) Conformationally restricted anti-plasmodial chalcones. Bioorg Med Chem Lett 15:4858–4861
Liu XL, Xu YJ, Go ML (2008) Functionalized chalcones with basic functionalities have antibacterial activity against drug sensitive Staphylococcus aureus. Eur J Med Chem 43:1681–1687
Mashevakaya IV, Anikina LV, Vikharev YB, Safin VA, Koltsova SV, Maslivets AN (2001) Synthesis and anti-inflammatory activity of the products of interaction of 4-aroyl-1,2-dihydro-4H-pyrrolo[5,1-c][1,4]benzoxazine-1,2,4-triones with 4-amino-1,2,4-triazole. Pharm Chem J 35:414–417
Mishra N, Arora P, Kumar B, Mishra LC, Bhattacharya A, Awasthi SK, Bhasin VK (2008) Synthesis of novel substituted 1 3-diaryl propenone derivatives and their antimalarial activity in vitro. Eur J Med Chem 43:1530–1535
Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Lijefors T (1998) Antileishmanial chalcones: statistical design, synthesis and three dimensional quantitative structure-activity relationship analysis. J Med Chem 41:4819–4832
Pandey VK, Yadava S, Chandra K, Joshi MN, Bajpai SK (1999) Antiviral activity of 7-arylamido/imidoalkyl-2,3-dihydro-2,3-diphenyl-1,3-benzoxazine-4-ones. Indian Drugs 36:532–534
Seigmund E, Cadmus R, Lu G (1957) A method for evaluating both non-narcotic and narcotic analgesics. Proc Soc Exp Biol 95:729–731
Tsuchiya H, Sato M, Akagiri M, Takagi N, Tanaka T, Iinuma M (1994) Anti-Candida activity of synthetic hydroxychalcones. Pharmazie 49:756–758
Waisser K, Gregor J, Dostal H, Kunes J, Kubicova L, Klimesova V, Kaustova J (2001) Influence of the replacement of the oxo function with the thioxo group on the antimycobacterial activity of 3-aryl-6,8-dichloro-2H-1,3-benzoxazine-2,4(3H)-diones and 3-arylquinazoline-2,4(1H, 3H)-diones. Farmaco 56:803–807
Waisser K, Kubicova L, Buchta V, Kubanova P, Bajerova K, Jiraskova L (2002) In vitro antifungal activity of 3-phenyl-2H-benzoxazine-2,4(3H)-diones. Folia Microbiol 47:488–492
Waisser K, Perina M, Kunes J, Klimesova V, Kaustova J (2003) 3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains. Farmaco 58:1137–1149
Winter CA, Risley EA, Nus GN (1962) Carrageenan induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc Soc Exp Biol 111:544–547
Wittmann S, Scherlitz-Hofmann I, Mollmann U, Ankel-Fuchs D, Heinisch L (2000) 8-Acyloxy-1,3-benzoxazine-2,4-diones as siderophore components of antibiotics. Arzneim-Forsch Drug Res 50:752–757
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One of the authors Mymooona Akhter is thankful to UGC for financial support. The authors are grateful to Janab Abdul Mueed for providing infrastructure and facility to carry out this work.
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Akhter, M., Habibullah, S., Hasan, S.M. et al. Synthesis of some new 3,4-dihydro-2H-1,3-benzoxazines under microwave irradiation in solvent-free conditions and their biological activity. Med Chem Res 20, 1147–1153 (2011). https://doi.org/10.1007/s00044-010-9451-x
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DOI: https://doi.org/10.1007/s00044-010-9451-x