Synthesis And Bioactivity Evaluation Of Novel Pyrazole Derivatives

The pyrazole framework plays an essential role in biologically active compounds. Many pyrazole derivatives are known to exhibit a wide range of biological properties such as anticoagulant,antipyretic,antibacterial,hypoglycaemic,antihy-perglycaemic,analgesic, anti-inflammatory,sedative-hypnotic,and antitumour activities.To find out new and effective biologically active drugs,much attention has been paid to synthesize pyrazole derivatives modified different groups.Using the nucleophilic substitute reaction of pyrazole,we intend to explore the influence of the substituent on aryl moiety and solvent on the yields of the reactions,to synthesize compounds with potent bioactivity and study the bioactivity of the obtained products. Four aspects were included in this paper:1.Ethyl 3-aryl-1H-pyrazole-5-carboxylate reacted with arylmethyl chloride in acetone or acetonitrile in the presence of potassium carbonate to afford 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives(3a-3i)in good yields.The structures of all products were confirmed by ¹H NMR,¹³C NMR,IR and MS spectra.2.We studied the bioactivity of 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives,and the biological evaluation results showed that the compounds 3a-3d promoted HUVEC apoptosis at the concentrations of(5-20)×10^-6mol·L^-1to a certain extent and the effect on the cell viability was dose-dependent. 3.Based on the obtained 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives,the hydrolysis reaction of the 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives with KOH alcohol solution afforded 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylic acid derivatives.4.The structures of the compounds(3c,4a,4c,4e)were further characterized by X-ray single crystal diffraction.In conclusion,we synthesized 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives and 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylic acid derivatives and then determined the structures of some products by X-ray single crystal diffraction method. Especially,we evaluated the biological activity of 1-arylmethyl-3-aryl-1H-pyrazole-5-carboxylate derivatives,which builds up the basis for us to investigate the operating mechanism of apoptosis induced by drugs in vascular endothelial cells,to study the structure-activity relationship,to design and synthesize more compounds with new structure and obvious effect.