公开(公告)号：US11897845B2

公开(公告)日：2024-02-13

申请号：US17572359

申请日：2022-01-10

Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  VANDERBILT UNIVERSITY ,  The UAB Research Foundation ,  The Trustees of the University of Pennsylvania

Inventor： David J. Maloney ,  Alex Gregory Waterson ,  Ganesh Rai Bantukallu ,  Kyle Ryan Brimacombe ,  Plamen Christov ,  Chi V. Dang ,  Victor Darley-Usmar ,  Xin Hu ,  Ajit Jadhav ,  Somnath Jana ,  Kwangho Kim ,  Jennifer L. Kouznetsova ,  William J. Moore ,  Bryan T. Mott ,  Leonard M. Neckers ,  Anton Simeonov ,  Gary Allen Sulikowski ,  Daniel Jason Urban ,  Shyh Ming Yang

IPC: C07D231/20 ,  C07D231/38 ,  C07D401/04 ,  C07D403/04 ,  C07D403/06 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D495/14 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5355 ,  A61K45/06 ,  A61K31/4178

CPC classification number: C07D231/20 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5355 ,  A61K45/06 ,  C07D231/38 ,  C07D401/04 ,  C07D403/04 ,  C07D403/06 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D495/14

Abstract: Provided is a compound of formula (I)




in which Ar1, R1, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

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：US20220144794A1

公开(公告)日：2022-05-12

申请号：US17602133

申请日：2020-04-09

Applicant: Vanderbilt University

Inventor： Gary A. Sulikowski ,  Christopher Fullenkamp ,  Kwangho Kim ,  Somnath Jana

IPC: C07D321/00 ,  A61P31/04

Abstract: Provided are 9-dechlorochrysophaentin analog compounds and the synthesis process thereof. The disclosed compound have remarkable antimicrobial activities that are comparable to, or even more potent than, the natural product chrysophaentin A. Also provided are method of inhibiting bacterial growth or treating bacterial infection by administering an effective amount of the disclosed compounds.

公开(公告)号：US11247971B2

公开(公告)日：2022-02-15

申请号：US17160868

申请日：2021-01-28

Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  VANDERBILT UNIVERSITY ,  The UAB Research Foundation ,  The Trustees of the University of Pennsylvania

Inventor： David J. Maloney ,  Alex Gregory Waterson ,  Ganesh Rai Bantukallu ,  Kyle Ryan Brimacombe ,  Plamen Christov ,  Chi V. Dang ,  Victor Darley-Usmar ,  Xin Hu ,  Ajit Jadhav ,  Somnath Jana ,  Kwangho Kim ,  Jennifer L. Kouznetsova ,  William J. Moore ,  Bryan T. Mott ,  Leonard M. Neckers ,  Anton Simeonov ,  Gary Allen Sulikowski ,  Daniel Jason Urban ,  Shyh Ming Yang

IPC: C07D231/20 ,  C07D231/38 ,  C07D401/04 ,  C07D403/04 ,  C07D403/06 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D495/14 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5355 ,  A61K31/4439 ,  A61K45/06

Abstract: Provided is a compound of formula (I), in which Ar1, R1, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

公开(公告)号：US10961200B2

公开(公告)日：2021-03-30

申请号：US16455848

申请日：2019-06-28

Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH ,  VANDERBILT UNIVERSITY ,  The UAB Research Foundation ,  The Trustees of the University of Pennsylvania

Inventor： David J. Maloney ,  Alex Gregory Waterson ,  Ganesh Rai Bantukallu ,  Kyle Ryan Brimacombe ,  Plamen Christov ,  Chi V. Dang ,  Victor Darley-Usmar ,  Xin Hu ,  Ajit Jadhav ,  Somnath Jana ,  Kwangho Kim ,  Jennifer L. Kouznetsova ,  William J. Moore ,  Bryan T. Mott ,  Leonard M. Neckers ,  Anton Simeonov ,  Gary Allen Sulikowski ,  Daniel Jason Urban ,  Shyh Ming Yang

IPC: C07D231/20 ,  C07D231/38 ,  C07D401/04 ,  C07D403/04 ,  C07D403/06 ,  C07D409/04 ,  C07D413/04 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5355 ,  A61K45/06 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D495/14

Abstract: Provided is a compound of formula (I) in which Ar1, R1, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

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：US10813355B2

公开(公告)日：2020-10-27

申请号：US16186106

申请日：2018-11-09

Applicant: Vanderbilt University

Inventor： Laurence Zwiebel ,  Gregory M. Pask ,  David C. Rinker ,  Ian M. Romaine ,  Gary A. Sulikowski ,  Paul R. Reid ,  Alex G. Waterson ,  Kwangho Kim ,  Patrick L. Jones ,  Robert W. Taylor

IPC: A01N43/653 ,  A01N43/82 ,  A01N43/78 ,  A01N43/90 ,  A01N25/08 ,  A01N47/16 ,  A01N47/18 ,  A01N53/00 ,  C07D249/12 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/06 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/048 ,  C07D491/052 ,  C07D491/056 ,  C07D513/04

Abstract: In one aspect, the invention relates to chemical modulators of insect olfactory receptors. In particular, compounds and compositions are provided that can inhibit sensory (e.g., host targeting) functions in airborne insects such as mosquitoes. Methods of employing such agents, and articles incorporating the same, are also provided. 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 invention.

公开(公告)号：US20200002285A1

公开(公告)日：2020-01-02

申请号：US16455848

申请日：2019-06-28

Applicant: The United States of America, as represented by the Secretary, Department of Health ,  Vanderbilt University ,  The UAB Research Foundation ,  The Trustees of the University of Pennsylvania

Inventor： David J. Maloney ,  Alex Gregory Waterson ,  Ganesh Rai Bantukallu ,  Kyle Ryan Brimacombe ,  Plamen Christov ,  Chi V. Dang ,  Victor Darley-Usmar ,  Xin Hu ,  Ajit Jadhav ,  Somnath Jana ,  Kwangho Kim ,  Jennifer L. Kouznetsova ,  William J. Moore ,  Bryan T. Mott ,  Leonard M. Neckers ,  Anton Simeonov ,  Gary Allen Sulikowski ,  Daniel Jason Urban ,  Shyh Ming Yang

IPC: C07D231/20 ,  C07D403/04 ,  C07D417/04 ,  C07D417/14 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5355 ,  A61K45/06 ,  C07D231/38 ,  C07D401/04 ,  C07D403/06 ,  C07D409/04 ,  C07D413/04 ,  C07D471/04 ,  C07D495/04 ,  C07D495/14

Abstract: Provided is a compound of formula (I) in which Ar1, R1, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

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：US10533010B2

公开(公告)日：2020-01-14

申请号：US15129042

申请日：2015-03-26

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 ,  A61K31/381 ,  A61K31/4045 ,  A61K31/498 ,  A61K31/551 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/14 ,  C07D409/12 ,  C07D409/14 ,  C07D471/04 ,  C07D209/42 ,  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.