Synthesis, physico-chemical properties and microsomal stability of compounds bearing aliphatic trifluoromethoxy group

J. Fluorine Chem. 2020, 231, 109461

DOI: 10.1016/j.jfluchem.2020.109461

Logvinenko I.; Markushyna Y.; Kondratov I.; Vashchenko B.; Kliachyna M.; Tokaryeva Y.; Pivnytska V.; Grygorenko O.; Haufe G.

Effects of the trifluoromethoxy substituent on physico-chemical properties of compounds, such as kinetic solubility, lipophilicity and microsomal clearance, was studied in a series of aliphatic derivatives. It was found that kinetic solubility of the CF3O-containing compounds was comparable to that of analogs, i.e. compounds bearing CH3O and CF3 moieties. The CF3O-substituted compounds had higher lipophilicity as compared to methoxy analogues, and nearly the same like CF3-bearing compounds. Microsomal stability studies indicated that the trifluoromethoxy group typically decreased metabolic stability of the corresponding derivatives as compared to either CH3O- or CF3-substituted counterparts, except for N-alkoxy(sulfon)amide series.