PMID: 9538520Apr 16, 1998Paper

Rational combinatorial library design. 1. Focus-2D: a new approach to the design of targeted combinatorial chemical libraries

Journal of Chemical Information and Computer Sciences
W ZhengA Tropsha

Abstract

We describe a new computational approach, called Focus-2D, to the rational design of targeted combinatorial chemical libraries. This approach is based on the hypothesis that structurally similar compounds display similar biological activity profiles. Building blocks that are used in a combinatorial chemical synthesis are randomly assembled to produce virtual library compounds. Individual library compounds are represented by Kier-Hall topological descriptors. Molecular similarities between compounds are evaluated quantitatively by modified pairwise Euclidean distances in multidimensional descriptor space. Simulated annealing is used to search the potentially large structural space of virtual chemical libraries to identify compounds similar to lead molecules. Frequency analysis of building block composition of selected virtual compounds identifies building blocks that can be used in combinatorial synthesis of chemical libraries with high similarity to the lead molecules. We show that this method correctly identifies building found in active peptoids with adrenergic or opioid activities.

Citations

Apr 8, 2019·Journal of Computer-aided Molecular Design·Oanh VuJens Meiler
Jul 18, 2002·Nature Reviews. Drug Discovery·Dimitris K AgrafiotisF Raymond Salemme
Dec 1, 2005·Drug Development and Industrial Pharmacy·Sanjay BajajA K Madan
Nov 5, 2019·Molecular Informatics·Philippe GantzerCarlos Nieto-Draghi
May 13, 2009·Journal of Chemical Information and Modeling·Hongming ChenTim Lange
May 5, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·J A BoutinJ L Fauchère
Jun 17, 2009·Journal of Chemical Information and Modeling·Peter S KutchukianEugene I Shakhnovich
Jan 25, 2003·Experimental Hematology·Ruiwu LiuKit S Lam
Aug 14, 2001·Journal of Chemical Information and Computer Sciences·L Chen, M W Deem
Dec 26, 2001·Journal of Chemical Information and Computer Sciences·C H ReynoldsW Zheng
Dec 26, 2001·Journal of Chemical Information and Computer Sciences·E T GrahamM G Cardozo
Aug 28, 1999·Journal of Medicinal Chemistry·J V de Julián-OrtizC Gimeno-Cardona
Jul 23, 2002·Journal of Chemical Information and Computer Sciences·Alexander GolbraikhAlexander Tropsha
Nov 7, 2019·Journal of Chemical Information and Modeling·Hongyao ZhuRobert V Stanton
May 10, 2005·Journal of Combinatorial Chemistry·Gang ChenHualiang Jiang
Jul 28, 2005·Journal of Chemical Information and Modeling·Jamal C SaehDavid A Cosgrove
Apr 13, 2000·Journal of Chemical Information and Computer Sciences·A Golbraikh
May 31, 2002·Journal of Medicinal Chemistry·Jayashree SrinivasanRobert V Stanton
Jul 25, 2006·Journal of Chemical Information and Modeling·Jean-François Truchon, Christopher I Bayly
Jan 27, 2004·Journal of Chemical Information and Computer Sciences·Nicolas BaurinLuc Morin-Allory
Jun 21, 2001·Journal of Chemical Information and Computer Sciences·E Estrada, E Molina
Jun 13, 2000·Journal of Chemical Information and Computer Sciences·R V StantonJ L Miller

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