| abstract |
Compounds, analogues of 3,4,6,8-substituted 2 - ([1,1'-biphenyl] -4-yl) quinoline analogs, which are inhibitors of dihydro-orotate dehydrogenase (DHODH), are disclosed in this document. with improved pharmacokinetic properties. The disclosed compounds can be used to treat a variety of disorders and diseases in which DHODH inhibition can be clinically useful, including cancer, such as hematological cancer, including acute myeloid leukemia (AML); graft-versus-host diseases; autoimmune disorders; and disorders associated with cell proliferationnT. The disclosed compounds can demonstrate flip-flop kinetics when administered orally, i.e., pharmacokinetics in which the absorption rate, rather than the elimination rate, dominates the pharmacokinetics. The disclosed compounds may demonstrate a sustained pharmacokinetic profile instead of an immediate release profile. This summary is intended to be a digitization tool for research purposes in the specific technique and is not intended to limit this disclosure. |