Inhibitors of mitochondrial pyruvate dehydrogenase kinase isoforms 1-4 and uses thereof
US10167258B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Dec 12, 2014 |
| Grant date | Jan 1, 2019 |
| Priority date | — |
| Expiry date | Dec 12, 2034 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D487/08
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present disclosure relates to the identification of PDK inhibitors and their use in the treatment of diseases such as diabetes, cardiovascular disease and cancer. The invention relates to the development of robust PDK inhibitors that can be used to improve glucose metabolism and correct metabolic dysfunction in vivo. Based on the unique structural features present in the ATP-binding pocket of PDK2, a single functional-group change was made in a known Hsp90 inhibitor that binds to the corresponding pocket of the latter protein from the GHKL family. This approach efficiently converted the Hsp90 inhibitor to a highly specific inhibitor for all PDK isoforms. These final PDK inhibitors of this series robustly augments PDC activity with reduced phosphorylation in tissues.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.