Impact of Fluoroalkyl Substituents on Physicochemical Properties of Saturated Heterocyclic Amines
Chemistry 2022, in progress
Profiling of the physicochemical properties (pKa , logP , and aqueous solubility) of fluoroalkyl-substituted heterocyclic amines was done to facilitate their rational application in medicinal chemistry research. The corresponding features of fluorine-containing compounds were compared to the parent non-fluorinated heterocycles and the corresponding fluorinated n -alkylamines. Amine basicity was observed to change in a monotonic fashion depending on the fluorination pattern. Although the introduction of fluoroalkyl groups had complex effects on lipophilicity and aqueous solubility of the compounds, possible contributions of the fluorination pattern, ring size, and conformational fixation of the substituent in the ring were addressed for a series of derivatives. The summarized data provides a useful guideline for application of fluorinated motifs for fine-tuning the compound’s properties related to drug discovery.