MULTI-COMPONENT SYNTHESIS OF HETEROCYCLIC FUSED PYRAZOLE SYSTEMS BASED ON 1,3-DIMETHYL PYRAZOL-5(4H)-ONDERIVATIVES AND THEIR ANTIPROLIFERATIVE EVALUATIONS

The multi-component reactions of 1,3-dimethyl pyrazol-5(4H)-one derivatives with different chemical reagents was illustrated through the preparation of novel heterocyclic fused pyrazole systems. A series of 42 novel fused pyrazole derivatives were synthesized through the multicomponent reactions. The new fused systems were thieno[3,2-c]pyrazole, pyrazolo[3,4-d]thiazole, pyrano[2,3-c]pyrazole, chromeno[2,3-c]pyrazole, benzo pyrano indazole and benzo chromeno indazole. The biological activity were evaluated for about 40 novel compounds as antiproliferative agents against six cancer cell lines and the results illustrated that compounds 5a, 5b, 7a, 7b, 9c, 9d, 9h, 9i, 11c, 11d and 18b were the most active compounds towards all the cancer cell lines used. Also, compounds 5c, 9g, 11a, 13b, 17a, 17d, 18a and 20b revealed high activity against the tested cancer cell lines. Foretinib was used as a standard reference drug in the evaluations. Moreover, the c-Met enzymatic activity and PC-3 inhibition were evaluated for all the prepared compounds.