The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

Meier, Kris; Bühlmann, Sven; Arús-Pous, Josep; Reymond, Jean-Louis (2020). The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery. CHIMIA, 74(4), pp. 241-246. Schweizerische Chemische Gesellschaft 10.2533/chimia.2020.241

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Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

Item Type:

Journal Article (Review Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Meier, Kris; Bühlmann, Sven Oliver; Arús Pous, Josep and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
500 Science

ISSN:

0009-4293

Publisher:

Schweizerische Chemische Gesellschaft

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

19 Jan 2021 10:57

Last Modified:

19 Jan 2021 11:06

Publisher DOI:

10.2533/chimia.2020.241

PubMed ID:

32331540

BORIS DOI:

10.48350/148849

URI:

https://boris.unibe.ch/id/eprint/148849

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