Fluorination Strategies for Improving Physicochemical and Biophysical Properties of Neurotherapeutics
Fluorination of a biological probe or therapeutic candidate perturbs the agent’s physicochemical and biophysical properties that influence pharmacodynamic, distribution, metabolism, and pharmacokinetic (DMPK) properties, and commonly improves overall drug-likedness. Because of these perturbations, roughly 30% of FDA approved therapeutics bear at least one fluorine atom, including 43% of newly approved small molecules in 2018. As such, synthetic strategies for accessing, as well as an intuition for exploiting, these fluorinated substructures is critical for modern drug-development.
In this research area, The Altman group’s work spans a spectrum of synthetic, organofluorine, organometallic, physical organic, and medicinal chemistries, and applies expertise in these fields to solve longstanding DMPK issues. Using two distinct classes of agents, namely endogenous peptides for modulating opioid pathways and natural product-derived agents for modulating serotonergic activity, the seminar will demonstrate: (1) the ability of modern synthetic reactions to enable access to fluorinated therapeutic candidates that were previously unattainable; (2) the power of fluorinated substructures to stabilize and improve drug-like properties of therapeutics candidates and biological probes.