Design based library

Library Design Based on Special Data Mining Algorithms... 

LIBRARY DESIGN BASED ON SPECIAL DATA MINING ALGORITHMS... 

In general, the described techniques provide an effective, flexible, and relatively fast solution for library design based on analysis of bioscreening data. The quantitative relationships, based on the assessment of contribution values of various molecular descriptors, not only permit the estimation of potential biological activity of candidate compounds before synthesis but also provide information concerning the modification of the structural features necessary for this activity. Usually these techniques are applied in the form of computational filters for constraining the size of virtual combinatorial libraries and... 

Stahl M. Structure-based library design. In Bohm HJ, Schneider G, editors. Virtual screening for bioactive molecules (Vol. 10 of Mannhold R, Kubinyi H, Timmerman H, editors. Methods and principles in medicinal chemistry). Wein-heim Wiley-VCH, 2000, pp. 229-64. 

Wyss PC, Gerber P, Hartman PG, Hubschwerlen C, Locher H, Marty HP, Stahl M. Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening. J Med Chem 2003 46 2304-12. 

Once the initial diversity fetish had run its course and management realized that it was inefficient to attempt to span the entirety of chemical space in search of drugs, more rational approaches based on chemoinformatics were developed to design combinatorial libraries and select candidates for screening on the basis of properties that have proven to be associated with successful therapeutics in the past. 

Plasmepsin II inhibitor, Ki 2 nM from structure-based library design... 

The integration of combinatorial chemistry, structure-based library design and virtual screening [268, 269] also resulted in successful applications [270, 271]. It ultimately should result in broader SAR information about directionality and physicochemical requirements of acceptable building blocks. This concept is based on feasible scaffolds for exploring protein subsites using parallel or combinatorial synthesis. 

The discovery of novel dihydrofolate reductase inhibitors by structure-based library design based on a 5-(dialkylamino)-2,4-diaminopyrimidine scaffold was reported by Wyss et al. [279] (cf Figure 4.5g). On the basis of a diaminopyrimidine core, a virtual... 

Bohm, H.-J. and Stahl, M. Stmcture-based library design molecular modeling merges with combinatorial chemistry. Curr. Opin. Chem. Biol. 2000, 4, 283-286. 

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