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本文引用的文献

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Analogues of 2-aminopyridine-based selective inhibitors of neuronal nitric oxide synthase with increased bioavailability.具有提高生物利用度的基于2-氨基吡啶的神经元型一氧化氮合酶选择性抑制剂类似物。
Bioorg Med Chem. 2009 Mar 15;17(6):2371-80. doi: 10.1016/j.bmc.2009.02.017. Epub 2009 Feb 14.
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Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping.通过片段跳跃发现高效且选择性的神经元型一氧化氮合酶抑制剂。
J Med Chem. 2009 Feb 12;52(3):779-97. doi: 10.1021/jm801220a.
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Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors.最小药效基团元素与片段跳跃，一种针对分子多样性和同工酶选择性的方法。选择性神经元型一氧化氮合酶抑制剂的设计。
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Predicting penetration across the blood-brain barrier from simple descriptors and fragmentation schemes.利用简单描述符和碎片化方案预测血脑屏障穿透性。
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A comparative study of bioorthogonal reactions with azides.叠氮化物生物正交反应的比较研究。
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Strategies to optimize brain penetration in drug discovery.药物研发中优化脑渗透的策略。
Curr Opin Drug Discov Devel. 2005 Jul;8(4):505-12.
8
Use of a physiologically based pharmacokinetic model to study the time to reach brain equilibrium: an experimental analysis of the role of blood-brain barrier permeability, plasma protein binding, and brain tissue binding.使用基于生理学的药代动力学模型研究达到脑平衡的时间：血脑屏障通透性、血浆蛋白结合和脑组织结合作用的实验分析
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The blood-brain barrier: an overview: structure, regulation, and clinical implications.血脑屏障：概述：结构、调节及临床意义
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Classification analysis of P-glycoprotein substrate specificity.P-糖蛋白底物特异性的分类分析
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选择性神经元型一氧化氮合酶抑制剂潜在胺前药对血脑屏障通透性的影响。

Effect of potential amine prodrugs of selective neuronal nitric oxide synthase inhibitors on blood-brain barrier penetration.

机构信息

Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, United States.

出版信息

Bioorg Med Chem. 2009 Nov 1;17(21):7593-605. doi: 10.1016/j.bmc.2009.08.065. Epub 2009 Sep 6.

DOI:10.1016/j.bmc.2009.08.065
PMID:19796958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2775413/
Abstract

Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood-brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications.

摘要

采取了几种前药方法来掩蔽含有伯胺或仲胺的两种强效和选择性神经元型一氧化氮合酶（nNOS）抑制剂中的氨基，以降低电荷并改善血脑屏障（BBB）穿透性。伯胺被掩蔽为叠氮化物，仲胺被掩蔽为酰胺或氨基甲酸酯。在各种体外和体内条件下，叠氮化物都不会还原为胺。尽管作为酰胺和氨基甲酸酯的氨基的电荷降低，但 BBB 穿透性并未增加。似乎叠氮化物作为伯胺的前药，酰胺和氨基甲酸酯作为仲胺的前药，对于 CNS 应用并不普遍有效。