Design,Synthesis And Activity Evaluation Of Dihydropyrimidinones,β-Carbonylamides And Xanthones

Cancer is one of the main causes of harm to human health.The incidence rate of cancer increases year by year on the global scale,which aggravates the urgency of finding suitable anticancer drugs.At present,the treatment of cancer mainly includes surgery,chemotherapy and radiotherapy,but for most tumors,chemotherapy is still the main treatment.Although there are many kinds of anti-tumor drugs,the curative effect is still not up to the ideal requirements,and the side effects are strong.Therefore,people are eager to find suitable,efficient,low toxic and highly selective antitumor drugs.Kinesin Eg5 is highly expressed in a variety of tumor cells,which is closely related to tumorigenesis and development.It has become a new target for antitumor drugs.In this study,kinesin Eg5 was selected as the target,dihydropyrimidinones,β-carbonylamides and xanthadiones are designed and synthesized.The research results show that:Under solvent-free conditions,the “multi-component one-pot method” for synthesis of target compounds has great synthetic advantages.17 dihydropyrimidones are synthesized.The reaction conditions were determined as follows: phosphoric acid0.1-0.15 m L,reaction temperature 100-110℃,the molar ratio of aromatic aldehyde: 1,3-dicarbonyl compound: methylurea / ethylurea = 1.0:1.0:1.1,reaction time 50-70 min.Among them,compounds A1,A2,A13 are the first reported new compounds.16 differentβ-carbonylamides are synthesized.The reaction conditions were determined as follows:lactic acid 0.15 m L,reaction temperature 110-120℃,the molar ratio of aromatic aldehyde:1,3-dicarbonyl compound = 1.0:1.2,reaction time 40-60 min.Among them,compounds B2-B10 and B16 are the first reported new compounds.10 different xanthadiones are synthesized.The reaction conditions were determined as follows: reaction temperature80-90℃,the molar ratio of aromatic aldehyde: 1,3-cyclohexanedione = 1:2.1,reaction time 40-60 min.Among them,compounds C3 and C9 are the first reported new compounds.The structures of the synthesized compounds were verified and characterized by X-Ray,HNMR,IR and other analytical instruments.The resulets showed that the synthesized compounds are consistent with the target compounds.The kinesin Eg5 was selected as an anti-tumor target for computer simulation,and the results showed that these compounds had certain inhibitory effects on kinesin Eg5.Finally,the compounds were initially tested for in vitro activity,and the results showed that compound A1,A2,A4,A6,A11,A15,B6,B9,B10,B13,B14 and B16 had a certain inhibitory effect on kinesin Eg5,but the inhibition rate was is low,the activity is poor.In this paper,43 target compounds were synthesized.At the same time,preliminary inhibition of Eg5 activity was measured,which provided a theory for the development of new antitumor drugs and practical basis.