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Chalcogen OCF 3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities
Author(s) -
Ghiazza Clément,
Billard Thierry,
Dickson Callum,
Tlili Anis,
Gampe Christian M.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900452
Subject(s) - chalcogen , adme , chemistry , combinatorial chemistry , drug , stereochemistry , organic chemistry , in vitro , pharmacology , biochemistry , medicine
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.