公开(公告)号：EP3793562A1

公开(公告)日：2021-03-24

申请号：EP19822319.0

申请日：2019-06-22

申请人： Ohio State Innovation Foundation ,  Hendrix College

发明人： BYRD, John C. ,  GOODWIN, Thomas E. ,  ELGAMAL, Ola ,  HERTLEIN, Erin ,  ABDULRAHIM, Mouad ,  BENNETT, Chad E. ,  VIBHUTE, Sandip Madhukar

IPC分类号： A61K31/519 ,  A61K45/06 ,  C07D215/12

公开(公告)号：EP4438042A2

公开(公告)日：2024-10-02

申请号：EP24181542.2

申请日：2019-06-22

申请人： Ohio State Innovation Foundation ,  Hendrix College

发明人： BYRD, John C. ,  GOODWIN, Thomas E. ,  ELGAMAL, Ola ,  HERTLEIN, Erin ,  ABDULRAHIM, Mouad ,  BENNETT, Chad E. ,  VIBHUTE, Sandip Madhukar

IPC分类号： A61K31/451

CPC分类号： A61K31/519 ,  A61K45/06 ,  A61K31/47 ,  A61P35/00 ,  A61K31/506 ,  A61K31/573 ,  A61K31/436 ,  A61K31/451 ,  C07D215/52 ,  A61P37/06 ,  A61P17/06

摘要： Disclosed herein are compounds, 3,4,6,8-substituted-2-([1,1'-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.