Chalcogen OCF 3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities

Clément Ghiazza , Thierry Billard (1) , Callum Dickson , Anis Tlili , Christian Gampe

1 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

The synthesis of SCF3 as well as SeCF3 isosteres of two OCF3-containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physico-chemical and ADME properties without introducing intrinsic liabilities. The Sand SeCF3 groups are more lipophilic than their O-parent; 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-CF3 groups as potential key players for future fluorinated pharmaceuticals.

Domaines: Chimie organique

Clément Ghiazza, Thierry Billard, Callum Dickson, Anis Tlili, Christian Gampe. Chalcogen OCF 3 Isosteres Modulate Drug Properties without Introducing Inherent Liabilities. ChemMedChem, 2019, 14 (17), pp.1586-1589. ⟨10.1002/cmdc.201900452⟩. ⟨hal-03035756⟩