Abstract
The present study described the design, synthesis and identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives. Their biological activity was tested for KATP channel opener as antihypertensives, COX-1 and COX-2 activity. The results were compared with the activity of cromakalim, ibuprofen and celecoxib. The study aimed at exploring the influence of introduction of a benzoxazine substituent at position 6 of various derivatives of benzopyrans in order to improve biological activity. Several compounds were found to be equipotent or even more potent than cromakalim. Out of these nitro-substituted benzopyrans, nitro substitution at benzoxazino group possessed potent antihypertensive activity in the R/S isomers. With amino derivatives, activity remains constant when compared with standard cromakalim. Similarly, compounds 17b, 17c, 17e and 17h have exhibited around 40 % inhibition of COX-1 as compared to the inhibition of COX-2. Only two compounds 17g and 17i exhibited effective inhibition more than 50 % of COX-2 compared with the inhibition of COX-1 at a concentration of 0.3 mg/ml.
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Acknowledgments
Authors would like to thank Institute of Pharmacy, Nirma University for providing necessary facilities for experimental work. Authors are thankful to SAIF, CDRI, Lucknow, for spectral analysis of the synthesized compounds. We are also thankful to Department of Science and Technology (DST) and Council of Scientific and Industrial Research (CSIR), India, for financial support.
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Bano, M., Barot, K.P., Jain, S.V. et al. Identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives as potassium channel activators and anti-inflammatory agents. Med Chem Res 24, 3008–3020 (2015). https://doi.org/10.1007/s00044-015-1344-6
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DOI: https://doi.org/10.1007/s00044-015-1344-6