公开(公告)号：US12144816B2

公开(公告)日：2024-11-19

申请号：US18064206

申请日：2022-12-09

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  James C. Tarr ,  KyuOk Jeon ,  James M. Salovich ,  Subrata Shaw ,  Nagarathanam Veerasamy ,  Kwangho Kim ,  Plamen P. Christov ,  Edward T. Olejniczak ,  Bin Zhao ,  Stephen W. Fesik ,  Zhiguo Bian

IPC: A61K31/551 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/538 ,  A61K45/06 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D487/04 ,  C07D519/00

Abstract: The present disclosure provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US20230330099A1

公开(公告)日：2023-10-19

申请号：US18064206

申请日：2022-12-09

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  James C. Tarr ,  KyuOk Jeon ,  James M. Salovich ,  Subrata Shaw ,  Nagarathanam Veerasamy ,  Kwangho Kim ,  Plamen P. Christov ,  Edward T. Olejniczak ,  Bin Zhao ,  Stephen W. Fesik ,  Zhiguo Bian

IPC: A61K31/551 ,  A61P35/00 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/538 ,  A61K45/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D487/04 ,  C07D519/00

CPC classification number: A61K31/551 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/538 ,  A61K45/06 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D487/04 ,  C07D519/00

Abstract: The present disclosure provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US10954193B2

公开(公告)日：2021-03-23

申请号：US15975854

申请日：2018-05-10

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Kwangho Kim ,  Plamen P. Christov ,  Johannes Belmar ,  Jason P. Burke ,  Edward T. Olejniczak ,  Stephen W. Fesik

IPC: C07D209/26 ,  A61K31/4045 ,  C07D401/14 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04 ,  C07D209/24 ,  A61K31/404 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/5377 ,  A61K45/06

Abstract: The present application, among other things, provides compounds that are capable of inhibiting the activity of anti-apoptotic Bcl-2 family proteins, for example, myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides pharmaceutical compositions as well as methods for using provided compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein. In some embodiments, a provided compound has the structure of formula I. In some embodiments, a provided compound has the structure of formula II.

公开(公告)号：US09949965B2

公开(公告)日：2018-04-24

申请号：US14885181

申请日：2015-10-16

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Jason P. Burke ,  Edward T. Olejniczak ,  Johannes Belmar ,  Zhiguo Bian ,  Stephen W. Fesik

IPC: A61K31/554 ,  A61K31/542 ,  A61K31/4745 ,  C07D513/06 ,  C07D471/08 ,  C07D498/06 ,  A61K31/5383 ,  A61K45/06

CPC classification number: A61K31/4745 ,  A61K31/5383 ,  A61K31/542 ,  A61K31/554 ,  A61K45/06 ,  C07D471/08 ,  C07D498/06 ,  C07D513/06

Abstract: The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US20160214934A1

公开(公告)日：2016-07-28

申请号：US14914307

申请日：2014-08-28

Applicant: VANDERBILT UNIVERSITY

Inventor： Taekyu Lee ,  Kwangho Kim ,  Plamen P. Christov ,  Johannes Belmar ,  Jason P. Burke ,  Edward T. Olejniczak ,  Stephen W. Fesik

IPC: C07D209/26 ,  A61K45/06 ,  C07D403/04 ,  A61K31/4155 ,  A61K31/5377 ,  A61K31/4439 ,  C07D413/04 ,  A61K31/422 ,  C07D401/14 ,  A61K31/404 ,  C07D401/04

CPC classification number: C07D209/26 ,  A61K31/404 ,  A61K31/4045 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/24 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D413/04

Abstract: The present application, among other things, provides compounds that are capable of inhibiting the activity of anti-apoptotic Bcl-2 family proteins, for example, myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides pharmaceutical compositions as well as methods for using provided compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein. In some embodiments, a provided compound has the structure of formula I. In some embodiments, a provided compound has the structure of formula II.

Abstract translation: 本申请尤其提供能够抑制抗凋亡Bcl-2家族蛋白（例如骨髓细胞白血病-1（Mcl-1））蛋白的活性的化合物。 本发明还提供药物组合物以及使用所提供的化合物治疗特征在于Mcl-1蛋白过度表达或失调的疾病和病症（例如癌症）的方法。 在一些实施方案中，所提供的化合物具有式I的结构。在一些实施方案中，所提供的化合物具有式II的结构。

公开(公告)号：US11596639B2

公开(公告)日：2023-03-07

申请号：US16081709

申请日：2017-03-03

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  James C. Tarr ,  KyuOk Jeon ,  James M. Salovich ,  Subrata Shaw ,  Nagarathanam Veerasamy ,  Kwangho Kim ,  Plamen P. Christov ,  Edward T. Olejniczak ,  Bin Zhao ,  Stephen W. Fesik ,  Zhiguo Bian

IPC: A61P35/00 ,  A61K45/06 ,  C07D487/04 ,  A61K31/551 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/538 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D519/00

Abstract: The present disclosure provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US11208415B2

公开(公告)日：2021-12-28

申请号：US16688872

申请日：2019-11-19

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Zhiguo Bian ,  Johannes Belmar ,  Plamen P. Christov ,  Nicholas F. Pelz ,  Subrata Shaw ,  Kwangho Kim ,  James C. Tarr ,  Edward T. Olejniczak ,  Bin Zhao ,  Stephen W. Fesik

IPC: C07D487/04 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/14 ,  C07D209/42 ,  A61K31/551 ,  A61K31/381 ,  A61K31/4045 ,  A61K31/498 ,  C07D409/14 ,  C07D471/04 ,  C07D409/12 ,  A61K31/404 ,  A61K31/4155 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14

Abstract: The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US10160763B2

公开(公告)日：2018-12-25

申请号：US15703289

申请日：2017-09-13

Applicant: Vanderbilt University

Inventor： Stephen W. Fesik ,  Shaun R. Stauffer ,  William P. Tansey ,  Edward T. Olejniczak ,  Jason Phan ,  Feng Wang ,  KyuOk Jeon ,  Rocco D. Gogliotti

IPC: C07D487/04 ,  C07B59/00

Abstract: Described are compounds that disrupt the WDR5-MLL1 protein-protein interaction, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating disorders and conditions in a subject.

公开(公告)号：US10093640B2

公开(公告)日：2018-10-09

申请号：US14429799

申请日：2013-09-20

Applicant: VANDERBILT UNIVERSITY

Inventor： Taekyu Lee ,  Nicholas F. Pelz ,  Johannes Belmar ,  Zhiguo Bian ,  Edward T. Olejniczak ,  Stephen W. Fesik ,  Brian A. Chauder

IPC: C07D307/85 ,  C07D405/10 ,  C07D413/10 ,  C07D401/10 ,  A61K31/381 ,  A61K31/343 ,  A61K31/404 ,  A61K31/4709 ,  A61K31/422 ,  A61K31/4439 ,  A61K31/4155 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  C07D403/12 ,  C07D401/14 ,  C07D405/14 ,  C07D333/70 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D409/04 ,  C07D413/04 ,  C07D413/12 ,  C07D471/04 ,  C07D209/42

Abstract: The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.

公开(公告)号：US20180086767A1

公开(公告)日：2018-03-29

申请号：US15703289

申请日：2017-09-13

Applicant: Vanderbilt University

Inventor： Stephen W. Fesik ,  Shaun R. Stauffer ,  William P. Tansey ,  Edward T. Olejniczak ,  Jason Phan ,  Feng Wang ,  KyuOk Jeon ,  Rocco D. Gogliotti

IPC: C07D487/04 ,  C07B59/00

CPC classification number: C07D487/04 ,  C07B59/002 ,  C07B2200/05

Abstract: Described are compounds that disrupt the WDR5-MLL1 protein-protein interaction, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating disorders and conditions in a subject.