公开(公告)号：US10287279B2

公开(公告)日：2019-05-14

申请号：US15048330

申请日：2016-02-19

申请人： THE GENERAL HOSPITAL CORPORATION ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services

发明人： Klaus Joachin Van Leyen ,  Theodore R. Holman ,  David J. Maloney ,  Ajit Jadhav ,  Anton Simeonov ,  Ganesha Rai

IPC分类号： C07D413/04 ,  C07D277/56 ,  C07D263/48 ,  A61K31/421 ,  A61K31/422 ,  A61K31/426 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/4245 ,  C07D277/42 ,  C07D213/85 ,  C07D239/42

摘要： A systematic screening has revealed a family of compounds that exhibit inhibitory effects on 12/15-lipoxygenase. Accordingly, the present invention relates to the use of these compounds for the inhibition of 12/15-lipoxygenase and for the treatment of a condition involving 12/15-lipoxygenase. Exemplary conditions include, but are not limited to, stroke, periventricular leukomalacia, cardiac arrest with resuscitation, atherosclerosis, Parkinson's disease, Alzheimer's disease, and breast cancer.

公开(公告)号：US20230257756A1

公开(公告)日：2023-08-17

申请号：US18020843

申请日：2021-08-09

申请人： The United States of America,as represented by the Secretary,Department of Health and Human Services

发明人： Mark J. Henderson ,  Michael H. Ronzetti ,  Bolormaa Baljinnyam ,  Tino W. Sanchez ,  Samuel G. Michael ,  Ashley E. Owens ,  Anton Simeonov

IPC分类号： C12N15/62 ,  C12N9/06 ,  C07K14/705 ,  C12N15/86 ,  G01N33/68

CPC分类号： C12N15/625 ,  C12Y101/01027 ,  C12Y105/01003 ,  C12N9/003 ,  C07K14/70596 ,  C07K14/70521 ,  C12N15/86 ,  G01N33/6845 ,  C12N2330/51

摘要： The disclosure provides methods for carrying out Real Time Cellular Thermal Shift Assays (RT-CETSA). Also provided are molecular constructs and protein constructs for use in such assays and devices suitable for carrying out such assays.

公开(公告)号：US11897845B2

公开(公告)日：2024-02-13

申请号：US17572359

申请日：2022-01-10

申请人： 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

发明人： 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分类号： 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分类号： 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

摘要： 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：US11247971B2

公开(公告)日：2022-02-15

申请号：US17160868

申请日：2021-01-28

申请人： 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

发明人： 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分类号： 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

摘要： 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：US11110089B2

公开(公告)日：2021-09-07

申请号：US15750817

申请日：2016-08-05

申请人： Elias Set Jenö Arnér ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

发明人： Elias Set Jenö Arnér ,  William Chester Stafford ,  Nathan Patrick Coussens ,  Diane Karen Luci ,  David Joseph Maloney ,  Anton Simeonov ,  Ajit Jadhav ,  Thomas S. Dexheimer

IPC分类号： C07D413/06 ,  A61K31/501 ,  A61K45/06

摘要： There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein W, X, Y, Z, R1, R2 and R3 have meanings provided in the description, which compounds are useful in the treatment of cancers.

公开(公告)号：US10881653B2

公开(公告)日：2021-01-05

申请号：US15750819

申请日：2016-08-05

申请人： Elias Set Jenö Arnér ,  The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： Elias Set Jenö Arnér ,  William Chester Stafford ,  Nathan Patrick Coussens ,  Diane Karen Luci ,  David Joseph Maloney ,  Anton Simeonov ,  Ajit Jadhav ,  Thomas S. Dexheimer

IPC分类号： A61K31/46 ,  A61P35/00 ,  C07D451/00

摘要： There is provided compounds of formula (I), or pharmaceutically-acceptable salts thereof, wherein X, Y, Z, R1 and R2 have meanings provided in the description, which compounds are useful in the treatment of cancers.

公开(公告)号：US08871789B2

公开(公告)日：2014-10-28

申请号：US13747406

申请日：2013-01-22

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： Thomas Michael Kristie ,  Yu Liang ,  Jodi Vogel ,  David J. Maloney ,  Ganesha Rai Bantukallu ,  Anton Simeonov ,  Ajit Jadhav

IPC分类号： A61K31/47 ,  A61K31/535 ,  A61K31/497 ,  C07D239/42 ,  A61K31/496 ,  A61K31/165 ,  A61K31/7088 ,  A61K31/505 ,  A61K31/44 ,  A61K45/06 ,  C07D215/14 ,  A61K31/198 ,  A61K31/166 ,  A61K31/195 ,  A61K31/135 ,  A61K31/00 ,  A61K31/225 ,  A61K31/551 ,  A61K31/137 ,  A61K31/194 ,  A61K31/506 ,  A61K31/444 ,  C07C233/56 ,  A61K31/5377

CPC分类号： A61K31/551 ,  A61K31/00 ,  A61K31/135 ,  A61K31/137 ,  A61K31/165 ,  A61K31/166 ,  A61K31/194 ,  A61K31/195 ,  A61K31/198 ,  A61K31/225 ,  A61K31/44 ,  A61K31/444 ,  A61K31/47 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/7088 ,  A61K45/06 ,  C07C233/56 ,  C07D215/14 ,  A61K2300/00

摘要： Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I): wherein R1, R2, R3, R4, and R5 are as defined herein or pharmaceutically acceptable salts thereof. Also disclosed is a method of preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the JMJD2 family of histone demethylases, for example, a compound of the formula (I). The viral infection may be a primary infection, reactivation of a virus after latency in a host, or may be in a mammal that has undergone, is undergoing, or will undergo immunosuppressive therapy.

摘要翻译： 公开了含有抑制JMJD2蛋白质的化合物和药物组合物，包括式（I）的化合物：其中R 1，R 2，R 3，R 4和R 5如本文所定义或其药学上可接受的盐。 还公开了一种预防或治疗宿主的病毒感染的方法，包括向宿主施用有效量的组蛋白脱甲基酶JMJD2家族抑制剂，例如式（I）化合物。 病毒感染可能是主要感染，宿主潜伏期后病毒的再活化，或可能在已经经历或将进行免疫抑制治疗的哺乳动物中。

公开(公告)号：US11505559B2

公开(公告)日：2022-11-22

申请号：US16760345

申请日：2018-10-30

申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  YALE UNIVERSITY

发明人： Shyh Ming Yang ,  David J. Maloney ,  Natalia Martinez ,  Adam Yasgar ,  Anton Simeonov ,  Vasilis Vasiliou

IPC分类号： C07D491/113 ,  C07D401/14 ,  C07D401/12 ,  C07D215/54 ,  C07D491/107 ,  C07D413/04 ,  C07D519/00 ,  C07D401/04 ,  C07D471/04 ,  C07D495/04 ,  C07D495/10 ,  C07D401/06 ,  C07D409/14

摘要： The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I.

公开(公告)号：US10899710B2

公开(公告)日：2021-01-26

申请号：US15750805

申请日：2016-08-05

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services ,  Elias Set Jenö Arnér

发明人： Elias Set Jenö Arnér ,  William Chester Stafford ,  Nathan Patrick Coussens ,  Diane Karen Luci ,  David Joseph Maloney ,  Anton Simeonov ,  Ajit Jadhav ,  Thomas S. Dexheimer

IPC分类号： C07D213/71 ,  A61P35/00 ,  A61K45/06

摘要： There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3, R4 and n have meanings provided in the description, which compounds are useful in the treatment of cancers.

公开(公告)号：US09802904B2

公开(公告)日：2017-10-31

申请号：US14655538

申请日：2013-12-26

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services ,  University of Delaware

发明人： David J. Maloney ,  Andrew S. Rosenthal ,  Ajit Jadhav ,  Thomas S. Dexheimer ,  Anton Simeonov ,  Zhihao Zhuang ,  Qin Liang ,  Diane K. Luci

IPC分类号： A61K31/505 ,  A61K31/506 ,  C07D239/42 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D239/94 ,  C07D405/14 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/048 ,  C07D495/04

CPC分类号： C07D239/94 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/048 ,  C07D495/04

摘要： Disclosed are inhibitors of the USP1/UAF1 deubiquitinase complex, for example. of formula (I), wherein R1, R2, and Q are as defined herein, which are useful in treating diseases such as cancer, and improving the efficacy of DNA damaging agents in cancer treatment. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of method of inhibiting a heterodimeric deubiquitinase complex in a cell, and a method of enhancing the chemotherapeutic treatment of cancer in a mammal undergoing treatment with an anti cancer agent. Further disclosed is a method of preparing compounds of the invention.