Synthesis and anthelmintic activity of benzopyrano[2,3- c ]pyrazol-4(2 H )-one derivatives

A series of benzopyrano[2,3- c ]pyrazol-4(2 H )-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1 H -pyrazol-3-ols by sequentially employing O -acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans . Five compounds, namely 2-phenyl[1]benzopyrano[2,3- c ]pyrazol-4(2 H )-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36 , 38 , 40 and 43 , respectively, altered the development of C. elegans . While the activities of 33 and 43 were rather modest, compounds 36 , 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40 , the active compounds have favourable toxicity profiles. Graphic abstract