Two classes of N'-(l,3-diaiy-1H--pyrazol-5-yl)-N,N-dimethylformamidine and N'-(4-formyl-l ,3-diaryl- 1H-pyrazol-5-yl)-N,N-dimethylformamidine were designed and synthesized by a chemoselective microwave-assisted amidination for evaluation of their difference of antiproliferative activities. A new chemoselective microwave irradiation of 5-amino-1,3 -disubstituted pyrazoles with N,N-methylformamide in the presence of POCl3 was successfully developed to alternatively synthesize presence of POCl3 was successfully developed to alternatively synthesize methnimidamides and pyrazolyl-2-azadienes two class compounds by using the tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Furthermore, the starting material 5-amino-l,3-disubstituted pyrazoles and de-amidination 5-amino-4-formyl-l,3-disubstituted pyrazoles were also used as the comparison molding cases for the structure activity relationship study. Following the SAR result, methnimidamide compounds 2b, 2c and 2d possessed the best potent with IC50 values in low micromolar range. On the other hand, We found the formyl group at C-4 position and the grafting amidinyl group in the pyrazolic main core molecule are necessary for the inhibitory activity.
