Systematic further development of caged prodrugs of protein kinase inhibitors by UV light and beta-irradiation

• Applicant: Professor Dr. Christian Peifer
• Subject Area: Pharmacy
• Term: from 2013 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242412745

The main objectives of the present application consist in a systematic further development and more detailed characterization of photo- and by beta-irrradiation activatable (so-called "caged") prodrugs of protein kinase inhibitors. On the basis of the established photo-pharmaceutical infrastructure and by our exciting results of the first application period we will continue to build a powerful medicinal-chemistry platform for caged prodrugs. Our approach will involve suitable scaffolds and kinase inhibitors for the photo- or by beta-irradiation activatable concept. Innovative applications for the control of drug release, optimization of inhibitor selectivity and efficacy, reduction of side effects and effective pharmacological tools can thus be developed. Activation of caged prodrugs by light showing a wavelength in the bio-optical window and in particular by beta-irradiation would enhance the tissue penetration thus providing significant therapeutic advantages. Using our knowledge it will then also be possible to develop caged inhibitors in the sense of a de novo design approach towards inhibitors of further kinase targets and beyond. Moreover, our results will be applicable to the photochemistry of protecting groups in particular for N-heterocycles.

• DFG Programme: Research Grants