Chalcogen OCF 3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities.

Autor: Ghiazza C; Institute of Chemistry and Biochemistry (ICBMS-UMR CNRS 5246), Université Lyon 1, CNRS, CPE-Lyon, INSA, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France., Billard T; Institute of Chemistry and Biochemistry (ICBMS-UMR CNRS 5246), Université Lyon 1, CNRS, CPE-Lyon, INSA, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France.; CERMEP-In vivo Imaging, Groupement Hospitalier Est, 59 Boulevard Pinel, 69003, Lyon, France., Dickson C; Novartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA., Tlili A; Institute of Chemistry and Biochemistry (ICBMS-UMR CNRS 5246), Université Lyon 1, CNRS, CPE-Lyon, INSA, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France., Gampe CM; Novartis Institutes for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2019 Sep 04; Vol. 14 (17), pp. 1586-1589. Date of Electronic Publication: 2019 Aug 21.
DOI: 10.1002/cmdc.201900452
Abstrakt: The synthesis of SCF 3 as well as SeCF 3 isosteres of two OCF 3 -containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF 3 and SeCF 3 groups are more lipophilic than their oxygen counterpart; however, microsomal stability is unchanged, indicating that these molecular changes may be beneficial for in vivo half-life. Enabled by modern synthetic methods, we present the chalcogen-CF 3 groups as potential key players for future fluorinated pharmaceuticals.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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