Virtual library design

The virtual library consists of three sublibraries an amide, a sulfonamide, and a urea library. High-throughput parallel synthesis strategies for the subHbraries are given elsewhere [133]. The schematic set-up of the virtual library is shown in Fig. 24. Examples of building blocks are given in Fig. 25. 

Three scaffolds (an amide, a sulfonamide, and a urea) are decorated with the same variable residues, R. The educt libraries include 26, 15, and 14 different reactants, respectively, which leads (combined with the three scaffolds) to a virtual library that comprises 16 380 compounds in total. In addition, 2779 high-potential thrombin inhibitors are identified (17%) by screening and virtual screening. 

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T5.W Data Reduction and Viewing for Virtual Library Design 407... 

Hits that are appealing to chemists as candidates for further optimization are often simple structures without excessive functionalizations this is due to the likelihood that complexity will increase during lead optimization [154]. A convenient way to gauge the potential attractiveness of a virtual library design is to compare molecular complexity scores of the virtual compounds to those calculated for hits that have been rated for their potential lead attractiveness by medicinal chemists. 

Van Drie, J. H. and Lajiness, M. S. (1998) Approaches to virtual library design. Drug Discovery Today 3, 274-283. 

Scaffold proposals were collected and reviewed according to privileged ion channel motifs, chemical feasibility, and fit to our multiple pharmacophores. Building block selection, virtual library design, and filtering yielded small virtual libraries suitable for automated solution-phase synthesis. All synthesized compounds were finally purified and characterized prior to addition to our focused library. 

Krovat, E. M., Fruhwirth, K. H., Langer, T. Pharmacophore identification, in silica screening, and virtual library design for inhibitors of the human factor Xa. J. Chem Inform. Model. 2005, 45, 146-159. 

J. H. van Drie and M. S. Lajiness, Drug Discovery Today, 3, 274 (1998). Approaches to Virtual Library Design. 

Fig. 4. Schematic illustration of virtual library design for library A.

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