辽宁大学学报（自然科学版）2024，Vol.51Issue(4)：298-314,17.
盐酸普环替尼(CY03529B)候选药物合成工艺优化研究
Study on Optimization of Synthetic Process of Candidate Drugs of Procyclitinib Hydrochloride(CY03529B)
周云鹏 1周利航 1唐明锐 1徐丹 1陈烨 1沈继伟1
作者信息
- 1. 辽宁大学 药学院,辽宁 沈阳 110036
- 折叠
摘要
Abstract
Chronic myeloid leukemia(CML)is a myeloproliferative disease caused by genetic mutations acquired from hematopoietic stem cells.As Tyrosine kinase inhibitors imatinib were approved by the Food and Drug Administration as clinical treatment of the disease,the problem of acquired drug resistance became more and more obvious,and the mutation of gene T315I was the most difficult to overcome.The second generation of Bcr-Abl tyrosine kinase inhibitors did not respond to the mutant,and the third generation inhibitors had good therapeutic effect but had great side effects.Therefore,by reviewing literatures and analyzing the eutectic structure of Type Ⅱtyrosine kinase inhibitors and Bcr-Abl kinase proteins,this research group designed and synthesized procyclitinib with tetrahydronaphthalene as its parent nucleus.Studies on cell activity and in vivo activity showed that it had better inhibitory effect on K562/G01 resistant cells and was superior to imatinib.In this process,6-methoxy-1-naphthomanone was used as the starting material to obtain procyclitinib hydrochloride through nucleophilic substitution,reduction,amide exchange and salt formation.On the basis of controlling the reaction material,the process parameters of each step were further investigated and optimized to achieve the synthesis process of procyclitinib hydrochloride,which was beneficial to scale-up production.The structure of the obtained product was confirmed by mass specturm(MS)and nuclear magnetic resonance hydrogen(1 H-NMR),and the results showed that the structure was correct.The whole process is short in time,simple in operation,low in cost,and the total yield is more than 26%.关键词
伊马替尼耐药/盐酸普环替尼/工艺参数/化学合成Key words
imatinib resistance/procyclitinib hydrochloride/process parameters/chemical synthesis分类
医药卫生引用本文复制引用
周云鹏,周利航,唐明锐,徐丹,陈烨,沈继伟..盐酸普环替尼(CY03529B)候选药物合成工艺优化研究[J].辽宁大学学报（自然科学版）,2024,51(4):298-314,17.
