Design and Synthesis of New Pyrazole-Based Heterotricycles and their Derivatization by Automated Library Synthesis.

Autor: Fricero P; Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK., Bialy L; Integrated Drug discovery, R&D, Sanofi Aventis Deutschland GmbH, Industriepark Höchst, 65926, Frankfurt am Main, Germany., Czechtizky W; Integrated Drug discovery, R&D, Sanofi Aventis Deutschland GmbH, Industriepark Höchst, 65926, Frankfurt am Main, Germany.; Present address: Respiratory, Inflammation, Autoimmunity IMED Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, SE-431 83, Gothenburg, Sweden., Méndez M; Integrated Drug discovery, R&D, Sanofi Aventis Deutschland GmbH, Industriepark Höchst, 65926, Frankfurt am Main, Germany., Harrity JPA; Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2020 Sep 03; Vol. 15 (17), pp. 1634-1638. Date of Electronic Publication: 2020 Jun 08.
DOI: 10.1002/cmdc.202000187
Abstrakt: Small-molecule heterocycles bearing orthogonal functionality have the potential to deliver diverse structural motifs that aid the drug-discovery effort. This work highlights how a readily assembled N-hydroxyethyl pyrazole trifluoroborate offers rapid access to architecturally distinct 5-6-6- and 5-7-6-fused tricyclic compounds. This chemistry is not only amenable to single compound synthesis, but also to high-throughput experimentation. It gives easy access to diverse compound arrays with various physicochemical and ADME profiles by fully automated library synthesis. The combination of the high-throughput experimentation with rapid testing of the compounds in an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds in drug-discovery projects.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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