Second-generation tricyclic pyrimido-pyrrolo-oxazine mTOR inhibitor with predicted blood-brain barrier permeability

Chiara Borsari; Erhan Keles; Andrea Treyer; Martina De Pascale; Paul Hebeisen; Matthias Hamburger; Matthias P Wymann

doi:10.1039/d0md00408a

Second-generation tricyclic pyrimido-pyrrolo-oxazine mTOR inhibitor with predicted blood-brain barrier permeability

RSC Med Chem. 2021 Jan 12;12(4):579-583. doi: 10.1039/d0md00408a.

Authors

Chiara Borsari¹, Erhan Keles¹, Andrea Treyer², Martina De Pascale¹, Paul Hebeisen^{1

3}, Matthias Hamburger², Matthias P Wymann¹

Affiliations

¹ Department of Biomedicine, University of Basel Mattenstrasse 28 4058 Basel Switzerland Matthias.Wymann@Unibas.ch.
² Pharmaceutical Biology, Pharmacenter, University of Basel Klingelbergstrasse 50 4056 Basel Switzerland.
³ PIQUR Therapeutics AG Hochbergerstrasse 60 4057 Basel Switzerland.

Abstract

Highly selective mTOR inhibitors have been discovered through the exploration of the heteroaromatic ring engaging the binding affinity region in mTOR kinase. Compound 11 showed predicted BBB permeability in a MDCK-MDR1 permeability in vitro assay, being the first pyrimido-pyrrolo-oxazine with potential application in the treatment of neurological disorders.