The strategic deployment of fluorine atoms in biologically active molecules is an increasingly common tactic in drug design and optimization. Among the different applications of fluorine in medicinal chemistry, one that continues to evolve is in the context of bioisosteric replacements. Although fluorine has long been utilized as a possible replacement for hydrogen, the incorporation of one or multiple fluorine atoms in more elaborate structural motifs can be exploited in the design of surrogate structures of several functional groups. One such example is the use of fluorine in the construction of carboxylic acid bioisosteres. To enable a direct comparison of the properties of fluorinated carboxylic acid surrogates with those of other commonly used, non-fluorinated bioisosteres we conducted a stucture property relationship (SPR) study based on matched molecular pair (MMP) analyses. Different fluorine containing carboxylic acid surrogates, including a series of fluorinated alcohols and phenols have been characterized by determining experimentally a series of physicochemical properties, such as acidity (pKa), lipophilicity (logP and logD7.4), permeability (PAMPA), as well as H-bonding.

Structure property relationship of fluorinated carboxylic acid bioisosteres

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.