Design, synthesis, antimicrobial, anti-inflammatory and analgesic activity of novel isoxazolyl pyrimido[4,5-b]quinolines and isoxazolyl chromeno[2,3-d] pyrimidin-4-ones

Novel series of 2-methyl-3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydropyrimido [4,5-b]quinolin-4-ones 5 and 3-(3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydro-2H-chromeno[2,3-d]pyrimidin-4-ones 7 have been synthesized from isoxazolyl cyanoacetamide synthon 2. Compound 2 was obtained by reaction of 4-amino-3-methyl-5-styrylisoxazole 1 with ethyl cyanoacetate. Isoxazolyl pyrimido[4,5-b]quinolin-4-ones 5 were obtained from compounds 2 by condensation with o-nitro benzaldehyde followed by treatment with SnCl2 and subsequent tandem N-acetylation and cyclodehydration with acetic anhydride. Compounds 2 were converted to isoxazolyl chromeno[2,3-d) pyrimidin-4-ones 7 by reaction with salicylaldehydes and subsequent cyclization with formaldehyde. Compounds 2-7 were characterized by IR, H-1 NMR, C-13 NMR, and Mass spectral data. The title compounds 5a-f and 7a-g were evaluated for their antimicrobial, anti-inflammatory and analgesic activity. Compounds 5d and 7e exhibited significant antimicrobial activity, potent anti-inflammatory and analgesic activities as that of standard drugs. (C) 2012 Elsevier Masson SAS. All rights reserved.