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Virtual Exploration of the Chemical Universe up to 11 Atoms of C, N, O, F:  Assembly of 26.4 Million Structures (110.9 Million Stereoisomers) and Analysis for New Ring Systems, Stereochemistry, Physicochemical Properties, Compound Classes, and Drug Discovery

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Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH-3012 Berne, Switzerland
Cite this: J. Chem. Inf. Model. 2007, 47, 2, 342–353
Publication Date (Web):January 30, 2007
https://doi.org/10.1021/ci600423u
Copyright © 2007 American Chemical Society
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    Abstract

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    All molecules of up to 11 atoms of C, N, O, and F possible under consideration of simple valency, chemical stability, and synthetic feasibility rules were generated and collected in a database (GDB). GDB contains 26.4 million molecules (110.9 million stereoisomers), including three- and four-membered rings and triple bonds. By comparison, only 63 857 compounds of up to 11 atoms were found in public databases (a combination of PubChem, ChemACX, ChemSCX, NCI open database, and the Merck Index). A total of 538 of the 1208 ring systems in GDB are currently unknown in the CAS Registry and Beilstein databases in any carbon/heteroatom/multiple-bond combination or as a substructure. Over 70% of GDB molecules are chiral. Because of their small size, all compounds obey Lipinski's bioavailability rule. A total of 13.2 million compounds also follow Congreve's “Rule of 3” for lead-likeness. A Kohonen map trained with autocorrelation descriptors organizes GDB according to compound classes and shows that leadlike compounds are most abundant in chiral regions of fused carbocycles and fused heterocycles. The projection of known compounds into this map indicates large uncharted areas of chemical space. The potential of GDB for drug discovery is illustrated by virtual screening for kinase inhibitors, G-protein coupled receptor ligands, and ion-channel modulators. The database is available from the author's Web page.

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     Corresponding author fax:  + 41 31 631 80 57; e-mail: [email protected].

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    Distribution of the highest atomic contribution of ring systems involved in the database construction process (Figure S1); list of filters applied during the structure generation process (Table S1); and descriptor value distribution profiles for GDB, RDB, and DMU (Figure S2). This information is available free of charge via the Internet at http://pubs.acs.org.

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