Combretastatin A-4 Class Of Anti-cancer Compound Design And Synthesis

Natural stilbenoids, including Combretastatin A-4, were found to be tubulin polymerization inhibitors and display strong antimitotic activity to a broad spectrum of human cancer lines. For the purpose of searching for new antitumor agents, we studied their 3D-QSAR (Three dimensions quantitative structure-activity relationship); furthermore, two new series of heteroeyclic compounds, known as the analogues of Combretastatin A-4, had been designed and synthesized.Two analogues of Combretastatin A-4 Compound I (4-(3, 4, 5-trimethoxyphenyl)-5-(3-hydroxyl-4-methoxyphenyl) - 1, 2, 3-thiadiazole) and CompoundⅡ(4-(3, 4, 5-trimethoxyphenyl)- 5-phenyl-)-1, 2, 3- thiadiazole), were designed. In the calculation of the CoMFA program, Compound I displayed good antimitotie activity. We applied 14-step and 5-step routes to synthesize CompoundⅠ～Ⅱ, and obtained overall yields of 6.7% and 34.3% respectively.In addition, two new CA-4 analogues of 3, 5-diphenyl-4, 5-dihydropyrazole-1-carboxamide (2-1～2-7) and 3, 5-diphenyl-4, 5-dihydropyrazole-1-carbothioamide (2-8～2-14) have been designed and synthesized.We developed a new method for the synthesis of 3, 5-diphenyl-1H-pyrazole analogue. In further research, this method could be developed into "one pot" procedure.