[EN] METHODS AND COMPOSITIONS FOR INHIBITION OF DIHYDROOROTATE DEHYDROGENASE<br/>[FR] MÉTHODES ET COMPOSITIONS POUR INHIBER LA DIHYDROOROTATE DÉSHYDROGÉNASE
申请人:OHIO STATE INNOVATION FOUNDATION
公开号:WO2021134042A1
公开(公告)日:2021-07-01
Disclosed herein are compounds, 6-substituted-2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid 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.