Methods and compositions for inhibition of dihydroorotate dehydrogenase
US11312686B2 · kind B2 · utility
Assignees
Inventors
Key dates
| Filing date | Jun 22, 2019 |
| Grant date | Apr 26, 2022 |
| Priority date | — |
| Expiry date | Jun 22, 2039 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61P37/06
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Disclosed herein are compounds, 3,4,6,8-substituted-2-([1′-biphenyl]-4-yl)quinoline analogs, that are inhibitors of dihydroorotate dehydrogenase (DHODH) with improved pharmacokinetic properties. The disclosed compounds can be used in the treatment of a variety of disorders and diseases in which inhibition of DHODH can be clinically useful, including cancer, such as a hematological cancer, including acute myeloid leukemia (AML); graft-versus-host-diseases; autoimmune disorders; and disorders associated with T-cell proliferation. The disclosed compounds can demonstrate flip-flop kinetics when administered orally, i.e., pharmacokinetics in which the rate of absorption, rather than the rate of elimination, dominates the pharmacokinetics. The disclosed compounds can demonstrate a sustained pharmacokinetic profile instead of an immediate release profile. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.