Abstract
Novel series of dihydro benzofuro[3,2-e]isoxazolo[4,5-b]azepin-5(5aH)-ones 6 have been synthesized from 3,5-dimethyl-4-nitroisoxazole 1. Compound 1 on treatment with salicyl aldehydes afforded the corresponding nitrostyrylisoxazoles 3, which upon reaction with ethyl bromo acetate followed by cyclization with triethylamine furnished ethyl 2,3-dihydro-3-[(3-methyl-4-nitro-5-isoxazolyl)methyl]benzofuran-2-carboxylates 5. Reductive cyclization of compounds 5 was effected with SnCl2–MeOH to give the title compounds 6. Compounds 4–6 were characterized by IR, 1H NMR, 13C NMR and Mass spectral data. The title compounds 6a–g were evaluated for their antimicrobial, anti-inflammatory, LOX-5 inhibitory, and analgesic activity. Compounds 6b and 6c exhibited significant antimicrobial activity, potent anti-inflammatory and analgesic activities as that of standard drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abd-Elazem IS, Chen HS, Bates RB, Huang RC (2002) Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase from Salvia miltiorrhiza. Antivir Res 55:91
Apers S, Vlietinck A, Pieters L (2003) Lignans and neolignans as lead compounds. Phytochem Rev 2:201
Chimichi S (1989) The preparation of coumaric acids via Styrylisoxazoles. Heterocycles 20:263–267
De Campos MP, Filho VC, Da Silva RZ, Yunes RA, Zacino S, Juarez S, Bella Cruz RC, Bella Cruz A (2005) Evaluation of antifungal activity of Piper solmsianum C. DC. var. solmsianum (Piperaceae). Biol Pharm Bull 28:1527
Krogsgaard-Larsen P, Falch E, Pedersen H (1988) Eu. Patent. Appl. No. 88310276
LaValle CR, Bravo-Altamirano K, Giridhar KV, Chen J, Sharlow E, Lazo JS, Pater W, Wang QJ (2010) Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC Chem Biol 10:1
Malla Reddy K, Rao CJ, Murthy AK (1981) Fused heterocycles IV. Synthesis of 7(O-hydroxyphenyl)-3,5-dimethyl 1-7,8-dihydro-6H-isoxazolo(4,5-b)azepines. Bull Chem Soc Jpn 54:361
Margery Linday E (1962) Practical introduction to microbiology. E. & F. N. Spon Ltd., New York, p 177
Martinez R (1980) The behaviour of 3-methyl-5-(o-r-styryl)-4-nitroisoxazoles under electron impact. I J Heterocyclic Chem 17:581–585
National committee for clinical laboratory standards (NCCLS) (1982) Standard methods for dilution antimicrobial susceptibility tests for bacteria, which grows aerobically; National committee for clinical laboratory standards Ltd. Villanova. 242
Pauletti PM, Araujo AR, Young MC, Giesbrecht AM, Bolzani VD (2000) Nor-Lignans from the leaves of Styrax ferrugineus (Styracaceae) with antibacterial and antifungal activity. Phytochemistry 55:597
Pieters L, Van Dyck S, Gao M, Bai R, Hamel E, Vlietinck A, Lemiere G (1999) Synthesis and biological evaluation of dihydrobenzofuran lignans and related compounds as potential antitumor agents that inhibit tubulin polymerization. J Med Chem 42:5475
Rajanarendar E, Nagi Reddy M, Rama Murthy K, Surendar P, Reddy RN, Reddy YN (2012a) Synthesis and in vitro and in vivo anticancer activity of novel phenylmethylene bis-isoxazolo[4, 5-b]azepinesBioorg. Med Chem Lett 22:149
Rajanarendar E, Raju S, Nagi Reddy M, Rama Krishna S, Hari Kiran L, Ram Narasimha Reddy A, Narasimha Reddy Y (2012b) Multi-component synthesis and in vitro and in vivo anticancer activity of novel arylmethylene bis-isoxazolo[4, 5-b]pyridine-N-oxides. Eu J Med Chem 50:274
Rajanarendar E, Nagi Reddy M, Govardhan Reddy K, Rama Krishna S (2012c) l-Proline catalyzed efficient one-pot three-component aza-Diels–Alder reactions on nitrostyryl isoxazoles: a facile synthesis of new isoxazolyl tetrahydroquinolines and isoxazolo[2, 3-a] pyrimidines. Tetrahedron Lett 53:2909
Rajanarendar E, Govardhan Reddy K, Rama Krishna S, Nagi Reddy M, Shireesha B, Durgaiah G, Reddy YN (2012d) Synthesis and in vitro and in vivo anticancer activity of novel 3-methyl-5H-isoxazolo[5′4′:5,6]pyrido[2,3-b]indoles. Bioorg Med Chem Lett 22:6677
Rao CJ, Murthy AK, Reddy PV (1981a) Mitotic inhibition & chromosomal damage induced by isoxazoloazepines in allium cepa meristematic cells. Indian Drugs Pharm Ind 25:265
Rao CJ, Murthy AK, Reddy MM, Swamy UB (1981b) Laboratary evaluation of isoxazoles against two pathogenic fungi-1: isoxazoloazepines. Indian Drugs Pharm Ind 1:322
Reddenna P, Whern J, Maddipati Reddy KR (1990) Purification of arachidonate 5-lipoxygenase from potato tubers. Methods Enzymol 187:268
Syamsudin F, Rahayn L (2010) HPLC analysis and pharmacokinetic study of mangostin after orally administration in rats. Int J Pharma Bio Sci 1(1):51–54
Ulusu NN, Ercil D, Salcar MK, Tezcan EE (2002) Abietic acid inhibits lipooxygenase activity. Phytother Res 16:88
Winter CA, Risley EA, Nuss GW (1990) Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Expt Biol Med 111:544–547
Acknowledgments
The authors are thankful to the Head, Department of Chemistry, Kakatiya University, Warangal for providing the facilities, the Director, Indian Institute of Chemical Technology, Hyderabad for recording 1H NMR, and Mass Spectral data. Financial assistance from the UGC SAP (phase-1)-DRS programme, New Delhi, India, is greatly acknowledged. We are grateful to Prof. J.R. Falck, Departments of Biochemistry and Pharmacology, University of Texas, Southwestern Medical Center, Texas, USA for helpful discussions. One of the authors (K. Govardhan Reddy) is thankful to UGC, New Delhi for financial assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rajanarendar, E., Govardhan Reddy, K., Rama Krishna, S. et al. Design, synthesis, antimicrobial, anti-inflammatory, and analgesic activity of novel dihydrobenzo furo[3,2-e]isoxazolo[4,5-b]azepin-5(5aH)-ones. Med Chem Res 22, 6143–6153 (2013). https://doi.org/10.1007/s00044-013-0598-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-013-0598-0