Synthesis and in vitro and in vivo anticancer activity of novel phenylmethylene bis-isoxazolo[4,5-b]azepines.

A series of novel phenylmethylene bis-isoxazolo[4,5-b]azepine derivatives (10) have been synthesized from 3-methyl-4-nitro-5-styrylisoxazoles 6. The reaction of 6 with 3,5-dimethyl-4-nitroisoxazole (7) in piperidine afforded the Michael type adducts 8, which on treatment with different substituted chalcones in the presence of piperidine gave the Michael adducts 9. Compounds 9 underwent reductive cyclization on treatment with SnCl(2)-MeOH to afford the title compounds 10. Structure of these compounds was established on the basis of IR, (1)H NMR, (13)C NMR and Mass spectral data. The title compounds 10a-j were evaluated for in vitro and in vivo anticancer activity. Compound 10j exhibited good anticancer activity as that of standard drug Cisplatin.