摘要
候选新药VPK是哈药集团技术中心自主研发治疗脑卒中的一类新药。VPK以长春西汀为母核,经水解、缩合、环化、成盐反应制备而成,经元素分析、核磁共振、高分辨质谱、X-射线粉末衍生,X-射线单晶衍射对化合物进行结构确证,经PDE1活性研究显示,VPK和长春西汀均对PDE1有抑制作用,其IC50值分别为17.40和1.97μmol·L^(-1),VPK在脑卒中治疗领域疗效较好,采用Caco-2单层细胞模型测定候选药物VPK吸收及外排转运特性,结果表明,VPK在顶端到基底端(A-B)及基底端到顶端(B-A)方向均表现高渗透,该供试化合物是外排转运体底物可能性较小。
The candidate drug VPK was category 1 of chemical drugs for stroke which was self-developed by Technology Center of Harbin Pharmaceutical Group. VPK was with vinpocetine as the mother nucleus and was obtained by reactions of hydrolysis, condensation, cyclization and salt-forming reaction. The structure of the compound was confirmed by elemental analysis, NMR, HRMS, X-ray powder diffraction, X-ray single crystal diffraction. Study based on the activity of PDE1 showed that both VPK and vinpocetine had inhibitory effects on PDE1, with the values of IC50 at 17.40 and 1.97 μmol· L-1, respectively, suggesting that VPK had better effect in the treatment of stroke. The characteristics of absorption and efflux transportation of candidate drug VPK was determined with Caco-2 single-layer cell model and the results had shown that VPK showed high permeability both in the apical-basal （A-B） direction and in the basal-apical （B-A） direction. There was little chance that the test compound was the substrate for efflux transporter, or it was not the substrate for efflux transporter.
作者
袁淑杰
丁辉
姜媛媛
夏吾炯
YUAN Shujie DING Hui JIANG Yuanyuan XIA Wujiong(School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, Chi- na Technology Center of Harbin Pharmaceutical Group, Harbin 150025, China)
出处
《东北农业大学学报》
CAS
CSCD
北大核心
2016年第10期25-33,共9页
Journal of Northeast Agricultural University
基金
黑龙江省抗肿瘤药物研制工程技术研究中心计划任务项目(GZ2013-45)
