Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles.
Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles.
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DOI：
10.1021/jacs.8b03187
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发表时间：
2018-05-30
影响因子：
15
通讯作者：
Denmark SE
中科院分区：
文献类型：
--
作者：
Barraza SJ;Denmark SE
含硅化合物在药物设计和开发中很大程度上被忽视了，尽管由于硅的独特特性，它们不仅可以改善药物的效力，还可以改善药物的物理化学和ADMET（吸收、分布、代谢、排泄、毒性）特性。这种缺陷在很大程度上是由于缺乏合成各种有机硅结构的通用方法。因此，一种新的构建块策略已经被开发出来，与传统的将硅纳入候选药物的方法不同。描述了灵活的、多克尺度的含硅四氢喹啉和四氢异喹啉构建块的合成，以及使用优化以适应硅性质的常见反应快速构建多种功能化含硅氮杂环的方法。此外，为了更好地阐明硅掺入的缺点和优点，在以admet为重点的生物学研究中，对选定的化合物及其碳类似物进行了挑战。
Silicon-containing compounds have been largely ignored in drug design and development, despite their potential to improve not only the potency but also the physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties of drug-like candidates because of the unique characteristics of silicon. This deficiency is in large part attributable to a lack of general methods for synthesizing diverse organosilicon structures. Accordingly, a new building block strategy has been developed that diverges from traditional approaches to incorporation of silicon into drug candidates. Flexible, multi-gram-scale syntheses of silicon-containing tetrahydroquinoline and tetrahydroisoquinoline building blocks are described, along with methods by which diversely functionalized silicon-containing nitrogen heterocycles can be rapidly built using common reactions optimized to accommodate the properties of silicon. Furthermore, to better clarify the liabilities and advantages of silicon incorporation, select compounds and their carbon analogues were challenged in ADMET-focused biological studies.
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影响因子：
1.1
作者：
BECKWITH, ALJ;EICHINGER, PH;PRAGER, RH
通讯作者：
PRAGER, RH
DOI：
10.1039/j29690000015
发表时间：
1969-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY B-PHYSICAL ORGANIC
影响因子：
--
作者：
EABORN, C;WALTON, DRM;YOUNG, DJ
通讯作者：
YOUNG, DJ
影响因子：
2.3
作者：
COOPER, BE;OWEN, WJ
通讯作者：
OWEN, WJ
DOI：
10.1039/j29710001446
发表时间：
1971-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY B-PHYSICAL ORGANIC
影响因子：
--
作者：
BAILEY, FP;TAYLOR, R
通讯作者：
TAYLOR, R
影响因子：
2.8
作者：
Daiss, JO;Burschka, C;Tacke, R
通讯作者：
Tacke, R