公开(公告)号：US20180258039A1

公开(公告)日：2018-09-13

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

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.

公开(公告)号：US10005728B2

公开(公告)日：2018-06-26

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

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.

公开(公告)号：US20160106731A1

公开(公告)日：2016-04-21

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

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.

Abstract translation: 本发明提供抑制抗凋亡Bcl-2家族成员骨髓细胞白血病-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。

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。