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TIN-一个组合化合物库,包含了可合成的多组分合成产物。

TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products.

机构信息

Molecular and Cellular Therapeutics Department, Royal College of Surgeons in Ireland , 123 St. Stephen's Green, Dublin 2, Ireland.

出版信息

J Chem Inf Model. 2011 May 23;51(5):986-95. doi: 10.1021/ci100443x. Epub 2011 Apr 15.

Abstract

The synthetic feasibility of any compound library used for virtual screening is critical to the drug discovery process. TIN, a recursive acronym for 'TIN Is Not commercial', is a virtual combinatorial database enumeration of diversity-orientated multicomponent syntheses (MCR). Using a 'one-pot' synthetic technique, 12 unique small molecule scaffolds were developed, predominantly styrylisoxazoles and bis-acetylenic ketones, with extensive derivatization potential. Importantly, the scaffolds were accessible in a single operation from commercially available sources containing R-groups which were then linked combinatorially. This resulted in a combinatorial database of over 28 million product structures, each of which is synthetically feasible. These structures can be accessed through a free Web-based 2D structure search engine or downloaded in SMILES, MOL2, and SDF formats. Subsets include a 10% diversity subset, a drug-like subset, and a lead-like subset that are also freely available for download and virtual screening ( http://mmg.rcsi.ie:8080/tin ).

摘要

用于虚拟筛选的任何化合物库的合成可行性对于药物发现过程至关重要。TIN 是“TIN 不是商业的”(TIN Is Not commercial)的递归缩写,是一种基于多样性导向多组分合成(MCR)的虚拟组合数据库枚举。使用“一锅法”合成技术,开发了 12 种独特的小分子支架,主要是苯乙烯异恶唑和双炔基酮,具有广泛的衍生潜力。重要的是,支架可以从含有 R 基团的商业上可获得的来源中通过单一操作获得,然后进行组合连接。这导致了一个包含超过 2800 万个产品结构的组合数据库,每个结构都是合成可行的。这些结构可以通过免费的基于 Web 的 2D 结构搜索引擎访问,也可以以 SMILES、MOL2 和 SDF 格式下载。子集包括 10%的多样性子集、药物样子集和先导样子集,也可免费下载和进行虚拟筛选(http://mmg.rcsi.ie:8080/tin)。

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