基于试剂的从头计算：探索化学空间的“点击，点击，环化”策略。
Reagent based DOS: a "Click, Click, Cyclize" strategy to probe chemical space.
机构信息
Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA.
出版信息
Org Biomol Chem. 2010 May 7;8(9):2198-203. doi: 10.1039/b927161a. Epub 2010 Mar 16.
Abstract
The synthesis of small organic molecules as probes for discovering new therapeutic agents has been an important aspect of chemical-biology. Herein we report a reagent-based, diversity-oriented synthetic (DOS) strategy to probe chemical and biological space via a "Click, Click, Cyclize" protocol. In this DOS approach, three sulfonamide linchpins underwent cyclization protocols with a variety of reagents to yield a collection of structurally diverse S-heterocycles. In silico analysis is utilized to evaluate the diversity of the compound collection against chemical space (PC analysis), shape space (PMI) and polar surface area (PSA) calculations.
摘要
小分子的合成作为发现新治疗剂的探针一直是化学生物学的一个重要方面。在此，我们报告了一种基于试剂的、多样化导向的合成（DOS）策略，通过“点击，点击，环化”方案来探测化学和生物空间。在这种 DOS 方法中，三个磺酰胺连接点与各种试剂进行环化反应，生成了一系列结构多样的 S-杂环化合物。通过计算化学空间（PC 分析）、形状空间（PMI）和极性表面积（PSA），利用计算机模拟分析来评估化合物库的多样性。
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