Spirocyclic scaffolds as fatty acid mimetics to improve solubility, bioavailability and selectivity

• Applicant: Professor Dr. Eugen Proschak
• Subject Area: Pharmacy ; Biological and Biomimetic Chemistry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 448583558

Endogenous fatty acid derivatives are involved in various physiological and pathophysiological processes in the context of metabolism and inflammation. Therefore, small molecules which are mimicking or antagonizing these effects, so-called fatty acid mimetics, are of special interest for drug discovery and development. In general, fatty acid mimetics exhibit favorable thermodynamic behavior and pharmacokinetic properties. However, the lipophilic nature of fatty acid mimetics complicates the optimization of solubility, bioavailability and selectivity. In this project, the use of spirocyclic scaffolds in the field of fatty acid mimetics shall be systematically investigated. For this purpose, scaffolds of lead structures for various targets of fatty acid mimetics will be replaced by their spirocyclic counterparts. The resulting lead pairs will be compared in terms of binding affinity, thermodynamics of binding, solubility, in vitro metabolic stability, in vitro bioavailability, and selectivity. The results will clarify whether spirocyclic cores are superior scaffolds in design and synthesis of fatty acid mimetics.

• DFG Programme: Research Grants
• International Connection: Russia
• Partner Organisation: Russian Foundation for Basic Research, until 3/2022
• Cooperation Partner: Professor Dr. Mikhail Krasavin, until 3/2022