文档介绍：四川大学硕士学位论文 5-***尿嘧啶衍生物的合成及抗癌活性初测姓名:吴林艳申请学位级别:硕士专业:药物化学指导教师:吴勇 20030510 摘要:5一***尿嘧啶衍生物的合成及抗癌活性研究导师:奖蛹教授硕士研究生:吴林撒 5一***联噱醚(5-FU)怒用于临床较早的一种肿瘤抑制荆。被摄入绷胞历,憨在分予瘩乎上}℃蛰i￡露霞落魏,掺入生秘天努予,警簸“蘩琵套袋”。在常见恶-隧肿瘤(特别咫时实体瘸j的潴疗中一直起着嚣嚣的作用,尤其在胃肠道肿瘸中的作用至今尚无其它药物能代替。然霹,}骚廉整_}{il 5。FU存在诸多缺点,始对癌纲擞低选择性,盘药浓度低等,俊5-FU呈现较高的副作用。多年来,入髓为菩找离教低毒斡5一***尿嘧啶衍生物进干亍了大量的研究。不少报道指出,连接5-FU和取代基之间的化学键的强度是影响5-FU前药性质的壤簧因素。该化学键即要有~定的稳定{生,袁生理琢境t}又饔麓拳舞陵去。。***尿嘧啶衍生物,通过在N—l傲酰化和0一O旺***取代口f入不同种类,不同长度的取代基米增强亲酯性、提高选择性、降低毒剥挥娜、提高治疗指数。形成在胃肠道可被吸收且不被破筇静翦嚣,并最终将在嚣常或辨瘙缀绞中转他为***漾跨啶。本课逖的另一方而,我们针对临床。L常见的骨肿瘸,设计将5-***尿嘧啶与骨靶向城体偕二:膦酸衍生物通过化学键偶联起来,得到化疗药物(5-FU)一锤二骥酸殛联耪,蓑戆进一步与被魅性棱索辍金,希望渡爨联物能靶向放、化疗骨胂瘸细胞,及骨显像、观察病变受攒的骨组织部位。本论文欺得到新化合物25个,其中5。***尿嘧啶衍生物18个,骨靶向配{奉3个,它们豹结卡句缀1{{.NMR、lR确证,抗癌生物滔性钵外筛选结果及髂拜费辩国往较好。芙键l鞲I:5一***尿嘧啶抗肿瘤药物抗癌生物活性骨肿瘤骨靶向二辨酸戆 ABS’rRACT:Study On thesynthesis and antitumor activity of5一Fluorouracil ’lutor:Pm￡Wu Ycmg Ma瓤erCandidate:Wu Linyan 5-Ftuorouracll{5一FU),8n analogue of uracil which inhibitsthymidylat# synthemse,has been widely usedclinically镕∞imfitamor agent(especially agaimt solidtumor).However,the therapeutic index01"5一FU is lowbecauseof itssideeffectsrsuch鹪poor tumor affinity,a low blood concentration of5·FU峨掰0,although ithas§strong antitamoreffect,Therefore,efforts hnvc been made tOsymhesize novel prodrug derivatives of5-FU possessing abroader spectrum ofantiturnoractivity with lessertoxioside effects than5-FU. As mentioned intheprevious documents,the bond slTength between the atom in the uraeitring and thesubstituem is an imtmrmnt factor influencing the antitumor activity andthetoxicity this assay,we report thesynthesis andantitumor activity ofl—alkyloyl-5-fluoranracil andt-(2"-oxyl)aⅡ啦l一孓i扭掰跏macil, On theotherside,in oonnecfion umors,we珙擞搬。矗to群q赋婚 conjugates of5*Fluorouracil(5-FrO withbisphosphonates which asli辨nds Call chelateradionuclides hope plexes exert bothbone-tar窑cted chemotherapeutic andradiotMrapeutio effects toward tumor can also_b。bonescanning agentsowing to 吐《chelatedradionuelides. In