Pickett S D, Luttmann C, Guerin V, Laoui A, James E
Rhône-Poulenc Rorer S. A., Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
J Chem Inf Comput Sci. 1998 Mar-Apr;38(2):144-50. doi: 10.1021/ci970060x.
Screening synthetic combinatorial libraries may facilitate rapid drug lead discovery by substantially increasing the number of molecules tested. Drug discovery efficiency and productivity can be further improved by designing libraries to maximize their molecular diversity or by comparing them to existing collections of compounds and/or libraries to select those that complement the properties already well represented. In this paper we describe two strategies to aid in the design and comparison of combinatorial libraries. The methods employ multi-pharmacophore three-dimensional (3D) descriptors in combination with two recent proposals for dissimilarity-based compound selection and library comparison. This method allows the design to be performed in product space and library comparison to consider all pair-wise intermolecular contributions to the diversity.
筛选合成组合文库可通过大幅增加测试分子的数量来促进快速发现药物先导物。通过设计文库以最大化其分子多样性，或者将它们与现有的化合物集合和/或文库进行比较以选择那些补充已充分代表的特性的文库，可以进一步提高药物发现的效率和生产力。在本文中，我们描述了两种有助于组合文库设计和比较的策略。这些方法采用多药效团三维（3D）描述符，并结合了两种基于差异的化合物选择和文库比较的最新提议。该方法允许在乘积空间中进行设计，并在文库比较中考虑所有成对分子间对多样性的贡献。
