The selective modulation of pharmacologically relevant physicochemical properties plays a critical role in the drug discovery process. The talk will delineate how the introduction of various substitution patterns of 1-3 fluorine atoms onto aliphatic side chains embedded within diverse scaffolds can offer significant advantages for property refinement. The presentation will highlight the effect of substitution on the modulation of basicity, intrinsic lipophilicity, aqueous solubility, and metabolic degradation by human liver microsomes. Importantly, while the preponderance of previous studies relies on comparison along the series CH2F, CHF2, and CF3, the talk includes comparison of additional structural isomers, such as CHFCHFCHF and CF2HCHF, which are otherwise lacking to date because of the difficulties associated with their synthesis.

Fluorination patterns and property modulation for drug discovery

256th National Meeting (2018)

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