Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery

The synthesis of a collection of
3-substituted indole derivatives
incorporating partially fluorinated n-propyl and n-butyl groups is described along with an in-depth study
of the effects of various fluorination patterns on their properties,
such as lipophilicity, aqueous solubility, and metabolic stability.
The experimental observations confirm predictions of a marked lipophilicity
decrease imparted by a vic-difluoro unit when compared
to the gem-difluoro counterparts. The data involving
the comparison of the two substitution patterns is expected to benefit
molecular design in medicinal chemistry and, more broadly, in life
as well as materials sciences.