| 药物与受体靶标结合动力学对体内药效的影响 |
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| 引用本文： | 郭 颖,郭宗儒.药物与受体靶标结合动力学对体内药效的影响[J].中国药物化学杂志,2014(1):70-77. |
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| 作者姓名： | 郭 颖 郭宗儒 |
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| 作者单位： | 中国医学科学院北京协和医学院药物研究所,北京100050 |
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| 摘 要： | 在新药研发的早期阶段,除了评价化合物对靶标的亲和力和选择性外,还有一个重要参数,即复合物的动力学性质,它与体内药效和安全性密切相关。化合物的离解常数K d或IC50是在封闭系统的平衡状态下测定的,而药物在体内处于开放系统,浓度和内环境在不断地变化,体外K d或IC50未必能够反映出体内靶标与药物结合的实际状态。复合物的离解速率不受游离药物浓度的影响,具有慢离解速率的药物(即长驻留时间的药物)对药理作用的持续时间、选择性作用和安全性有重要影响。本文简要叙述药物结合动力学原理以及影响结合和离解速率的结构特征,并举例说明结合动力学在新药创制中的意义。
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| 关 键 词： | 结合动力学 驻留时间 慢离解速率 新药创制 |
Improved synthesis of retigabine |
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| Institution: | ZHU Lei^1, WANG Jia-le^1 , WANG Pu-hai^2. ( 1. School of Pharmaceutical Sciences ,Nanjing University of Technology ,Nanjing 211816, China ; 2. Jiangsu Institute of Materia Medica , Nanjing University of Technology ,Nanjing 211816, China) |
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| Abstract: | Retigabine, as a new kind of mechanism of action of potassium ion channel opener, was used for anti-epileptic. In this paper, a six-step procedure from p-nitrophenylamine as starting material was used to synthesize the desired compound through a series of reactions, such as substitution, reduction, protection, ni tration, deprotection, addition and elimination reaction and reduction. The process expressed a higher selectiv ity than that of the former methods described, and the overall yield was 62 %. The structure of retigabine was characterized by IR, ~H-NMR, ~3C-NMR and HRMS （ESI）. The improved process has the advantages of low cost, high selectivity and mild reaction for industrial production. |
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| Keywords: | retigabine anti-epileptic drug process improvement |
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