CAJ | 학술논문

目的：以他克林（ Terrine，THA）为母药，合成具备脑靶向性的化学传输系统（ CDs）。方法选用溴乙酰氯与THA共价连接，再与烟酰肼烷基化后，用溴乙酸乙酯与其形成季铵盐，最后将其还原成二氢吡啶载体介导的前体药物。结果制备所得的化合物经1 HNMR、MS 进行结构表征，确认为目标化合物（TM）。 TM脂溶性Rm值由THA的1.75提高至2.87。体外12h母药累积释放量达到81.8％。结论新型二氢吡啶载体介导的前体药物较THA更易于穿透BBB。药物体外释放研究预示TM在脑组织可缓慢释放出母药，平稳地发挥药效。
목적：이타극림（ Terrine，THA）위모약，합성구비뇌파향성적화학전수계통（ CDs）。방법선용추을선록여THA공개련접，재여연선정완기화후，용추을산을지여기형성계안염，최후장기환원성이경필정재체개도적전체약물。결과제비소득적화합물경1 HNMR、MS 진행결구표정，학인위목표화합물（TM）。 TM지용성Rm치유THA적1.75제고지2.87。체외12h모약루적석방량체도81.8％。결론신형이경필정재체개도적전체약물교THA경역우천투BBB。약물체외석방연구예시TM재뇌조직가완만석방출모약，평은지발휘약효。
OBJECTIVE In order to improve the brain targeted ability of tacrine ( THA ) , a brain targeted chemical delivery system ( BTCDs ) was synthesized.METHODS THA was firstly linked with Chloroacetyl bro-mine,and then with nicotinic acid hydrazide ,finally pyridine quaternary ammonium was prepared though bromoace-tate and deoxidized to the dihydropyridine carrier-mutual prodrug.RESULTS CDs was synthesized successfully and its′structure were identified by 1 HNMR and MS,the lipophilicity of BTCDs was increased from 1.75 ( THA) to 2.87.Drug release percentage in brain homogenate was 81.8% in vitro in 12 h.CONCLUSION It indicates that this dihydropyridine carrier-mutual prodrug ,which can be provided with a good brain-targeting and slow release prop-erty,is a promising brain targeting drug.