Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries.
Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries.
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DOI：
10.1111/j.1747-0285.2011.01100.x
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发表时间：
2011-05
影响因子：
3
通讯作者：
Medina-Franco JL
中科院分区：
文献类型：
--
作者：
López-Vallejo F;Nefzi A;Bender A;Owen JR;Nabney IT;Houghten RA;Medina-Franco JL
组合文库在药物发现中继续发挥关键作用。为了增加结构多样性，已经开发了几种实验方法。然而，有限的努力已经执行到目前为止，以量化广泛使用的多样性为导向的合成（DOS）库的多样性。在这里，我们报告了一个全面的表征15双-二氮杂环组合库通过图书馆从图书馆，这是一个DOS的方法。使用MACCS键，径向和不同的药效指纹图谱以及六个分子特性，它被证明增加的结构和性能的多样性的图书馆从图书馆超过个别图书馆。将文库与现有药物、NCI Diversity和Molecular Libraries Small Molecule Repository的比较揭示了组合文库的结构独特性（对于任何指纹表示，平均相似性< 0.5）。特别是，双环硫脲库在结构上最不相似的药物保留药物样特征的属性空间。这项研究代表了图书馆的多样性的第一次全面量化，提供了一个坚实的定量方法来比较和对比DOS图书馆与现有药物或任何其他化合物的多样性。
Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic (DOS) libraries. Herein we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a DOS approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI Diversity and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity < 0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of DOS libraries with existing drugs or any other compound collection.
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影响因子：
3
作者：
Medina-Franco, Jose L.;Maggiora, Gerald M.;Houghten, Richard A.
通讯作者：
Houghten, Richard A.
影响因子：
5.6
作者：
Fink, Tobias;Reymond, Jean-Louis
通讯作者：
Reymond, Jean-Louis
影响因子：
3.5
作者：
Martinez-Mayorga, Karina;Medina-Franco, Jose L.;Houghten, Richard A.
通讯作者：
Houghten, Richard A.
影响因子：
14.8
作者：
Hert, Jerome;Irwin, John J.;Laggner, Christian;Keiser, Michael J.;Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.
DOI：
10.1021/ci000091j
发表时间：
2001-01-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Agrafiotis, DK
通讯作者：
Agrafiotis, DK