Synthesis And Structural Analysis Of The Antitumor Compounds 1-(Benzyl)-3-phenylhydrea Derivatives

Hydrea(HU),which is also called hydroxylcarbamide,is a kind of inhibitors of ribonucleoside diphosphate reductase.And it is also the only antitumor drug of RRIs in clinical.Its indications include treatments for ? Mediterranean disease,melanoma,myelogenous leukemia,tumor of the ovary and so on.In addition,in addition,Hydrea can still give treatment for sickle cell anemia and inhibit replication of virus of HIV.But because of the shortcomings that its ClogP is low,the molecular polarity is too big and half-life in the human body is short,additionally,HU has inherent toxicity which have the carcinogenic action to human body.Therefore it is necessary for us to carry out their structure transform,increase its liposolubility,reduce its toxicity and prolong the half-life.This paper focuses on the Synthesis of the antitumor Compounds of 1-(Benzyl)-3-phenylhydrea Derivatives and studies of their structure.And sttudy the antitumor activities of hydrea derivatives which have been synthesized,we investigated the effect to the K562 which is leukemia cell of human,L1210 which is leukemia cells of mice and HEP-2 which is laryngocarcinoma cells of human.In addition,we made a preliminary analysis of the relationship of its structure-activity according to the function of these compounds to tumor cells.This thesis mainly includes the following aspects:First,the cuent situation of the cancer,the function mechanism of antitumor of hydrea,the clinical use of hydrea and its limitations.Second,through the review of the literature,puts forward a synthesis route of 1-(Benzyl)-3-phenylhydrea derivatives and got the target compounds successfully.I totally synthesized 21 hydrea derivatives,through the inquest by CA,in addition that the compound YB1 has reported,the others are all new compounds which are not reported.And determined the structure of the target compounds by the research of IR?MS?1H-NMR and 13C-NMR.Third,we made the structure basis of the target compounds by 1H-NMR 13C-NMR IR and MS map,and carried on the comprehensive analysis with the comprehensive information of charts.Fourth,we made the antitumor activity screening of hydrea derivatives with the method of MTT,we investigated the effect to the K562 which is leukemia cell of human,L1210 which is leukemia cells of mice and HEP-2 which is laryngocarcinoma cells of human.The vitro activity results show that there are some target compounds whose cell activity are better than the cell activity of hydrea which conduct as the positive control medicine,such as the activity of compound YB4(IC50 = 80.60 u mol/1)to the HEP-2 which is laryngocarcinoma cells is far higher than the activity of hydrea(IC50 = 192.00 u mol/1);and the activity of compound YB1(IC50 = 17.70 u mol/1),YB2(IC50 = 21.00 u mol/1),YB4(IC50 = 57.00 u mol/1),and YB5(IC50 =60.30 u mol/1)to K562 which is leukemia cell are far higher than the activity of hydrea(IC50 = 73.60 u mol/1).Finally,we made a preliminary analysis of the relationship of its structure-activity according to the function of these compounds to tumor cells.