The reaction of cyanoacetylhydrazine (1) with 3-(2-bromoacetyl)-2H-chromen-2-one (2) in 1,4-dioxan gave the hydrazidehydrazone derivative (3). The latter compound was cyclized to the 1,3,4-oxadiazine derivative 4, its 4-bromo derivative underwent a series of cross coupling reactions together with [4+2] cycloaddition reactions with either acrylonitrile or ethyl acrylate to afford the pyran derivatives 10a and 10b, respectively. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Four of the synthesized compounds namely 7c, 10a, 11a and 12b showed high inhibitory effects. Moreover, the anti-leishmanial activity of the newly synthesized product was tested on Leishmania donovani amastigotes showed that some compounds have high activity.