公开(公告)号：US10336734B2

公开(公告)日：2019-07-02

申请号：US15748214

申请日：2016-08-02

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Nupam P. Mahajan ,  Kiran N. Mahajan ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： A61K31/506 ,  C07D405/12 ,  C07D403/12 ,  C07D405/14 ,  C07D401/12 ,  C07D239/48 ,  A61P35/00

摘要： Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of ACK1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new ACK1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I are disclosed.

公开(公告)号：US10106507B2

公开(公告)日：2018-10-23

申请号：US15501613

申请日：2015-08-03

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Ernst Shönbrunn ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D239/48 ,  A61K31/505 ,  A61K45/06 ,  A61K31/506 ,  A61K31/5377 ,  C07D405/12 ,  C07D239/95 ,  A61K31/517 ,  C07D239/70 ,  C07D491/048 ,  A61K31/519 ,  C07D401/12 ,  C07D403/12 ,  C07D401/14

摘要： Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.

公开(公告)号：US20180215742A1

公开(公告)日：2018-08-02

申请号：US15882094

申请日：2018-01-29

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Harshani R. Lawrence ,  Said M. Sebti ,  Sevil Ozcan

IPC分类号： C07D413/04 ,  C07D271/04 ,  C07D271/06

CPC分类号： C07D413/04 ,  C07D271/04 ,  C07D271/06

摘要： Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).

公开(公告)号：US10526291B2

公开(公告)日：2020-01-07

申请号：US16166611

申请日：2018-10-22

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Ernst Schönbrunn ,  Nicholas J. Lawrence ,  Harshani R. Lawrence ,  Gary W. Reuther

IPC分类号： C07D401/14 ,  C07D239/48 ,  C07D403/12 ,  C07D401/12 ,  C07D405/12 ,  C07D239/70 ,  C07D239/95 ,  C07D491/048 ,  A61K31/505 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  A61K45/06

摘要： Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.

公开(公告)号：US20180290984A1

公开(公告)日：2018-10-11

申请号：US15767676

申请日：2016-10-13

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Ernst Schönbrunn ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D239/48 ,  A61P35/00

CPC分类号： C07D239/48 ,  A61K45/06 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D491/048

摘要： Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I through IV.

公开(公告)号：US10017478B2

公开(公告)日：2018-07-10

申请号：US15808421

申请日：2017-11-09

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Nupam P. Mahajan ,  Kiran N. Mahajan ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D405/12 ,  C07D239/49 ,  C07D239/42 ,  C07D405/14 ,  C07C53/18 ,  C07D239/48

CPC分类号： C07D239/49 ,  A61P35/00 ,  C07C53/18 ,  C07D239/42 ,  C07D239/48 ,  C07D405/12 ,  C07D405/14

摘要： Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

公开(公告)号：US09878999B2

公开(公告)日：2018-01-30

申请号：US14035453

申请日：2013-09-24

申请人： H. Lee Moffitt Cancer Center and Research Institute, Inc.

发明人： Harshani R. Lawrence ,  Said M. Sebti ,  Sevil Ozcan

IPC分类号： A61K31/497 ,  C07D413/04 ,  C07D271/04 ,  C07D271/06

CPC分类号： C07D413/04 ,  C07D271/04 ,  C07D271/06

摘要： Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).

公开(公告)号：US11643396B2

公开(公告)日：2023-05-09

申请号：US16894010

申请日：2020-06-05

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Ernst Schönbrunn ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D239/48 ,  C07D491/048 ,  C07D405/14 ,  C07D403/12 ,  C07D405/12 ,  C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  A61P35/00 ,  A61K45/06

CPC分类号： C07D239/48 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D491/048 ,  A61K45/06

摘要： Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I through IV.

公开(公告)号：US10738016B2

公开(公告)日：2020-08-11

申请号：US15767676

申请日：2016-10-13

申请人： H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

发明人： Ernst Schönbrunn ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D239/48 ,  C07D491/048 ,  C07D405/14 ,  C07D403/12 ,  C07D405/12 ,  C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  A61P35/00 ,  A61K45/06

摘要： Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I through IV.

公开(公告)号：US20180155297A1

公开(公告)日：2018-06-07

申请号：US15808421

申请日：2017-11-09

申请人： H. Lee Moffitt Cancer Center And Research Institute, Inc.

发明人： Nupam P. Mahajan ,  Kiran N. Mahajan ,  Nicholas J. Lawrence ,  Harshani R. Lawrence

IPC分类号： C07D239/49 ,  C07D405/12 ,  C07D239/42 ,  C07D239/48 ,  C07C53/18 ,  C07D405/14

CPC分类号： C07D239/49 ,  C07C53/18 ,  C07D239/42 ,  C07D239/48 ,  C07D405/12 ,  C07D405/14

摘要： Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.