公开(公告)号：US20230312511A1

公开(公告)日：2023-10-05

申请号：US18111241

申请日：2023-02-17

申请人： The United States of America, as represented by the Secretary, Department of Health and Human ,  The University of Kansas ,  The University of North Carolina at Chapel Hill

发明人： David R. Sibley ,  Amy Elizabeth Moritz ,  R. Benjamin Free ,  Joseph P. Steiner ,  Noel Terrence Southall ,  Marc Ferrer ,  Xin Hu ,  Warren S. Weiner ,  Jeffrey Aubé ,  Kevin Frankowski

IPC分类号： C07D401/12 ,  A61P25/28 ,  C07D209/42 ,  C07D213/65 ,  C07D213/81 ,  C07D235/24 ,  C07D295/185 ,  C07D307/85 ,  C07D317/64 ,  C07D333/70 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04

CPC分类号： C07D401/12 ,  A61P25/28 ,  C07D209/42 ,  C07D213/65 ,  C07D213/81 ,  C07D235/24 ,  C07D295/185 ,  C07D307/85 ,  C07D317/64 ,  C07D333/70 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04

摘要： The disclosure of a compound of Formula I or a pharmaceutically acceptable salt thereof




The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula I together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula I is administered to the patient together with one or more additional active agents.

公开(公告)号：US11634404B2

公开(公告)日：2023-04-25

申请号：US16093365

申请日：2017-04-14

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services ,  The University of Kansas ,  The University of North Carolina at Chapel Hill

发明人： David R. Sibley ,  Amy Elizabeth Moritz ,  R. Benjamin Free ,  Joseph P. Steiner ,  Noel Terrence Southall ,  Marc Ferrer ,  Xin Hu ,  Warren S. Weiner ,  Jeffrey Aubé ,  Kevin Frankowski

IPC分类号： C07D401/12 ,  A61P25/28 ,  C07D295/185 ,  C07D209/42 ,  C07D213/65 ,  C07D213/81 ,  C07D235/24 ,  C07D307/85 ,  C07D317/64 ,  C07D333/70 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04

摘要： The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.

公开(公告)号：US20210323941A1

公开(公告)日：2021-10-21

申请号：US16093365

申请日：2017-04-14

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

发明人： David R. Sibley ,  Amy Elizabeth Moritz ,  R. Benjamin Free ,  Joseph P. Steiner ,  Noel Terrence Southall ,  Marc Ferrer ,  Xin Hu ,  Warren S. Weiner ,  Jeffrey Aubé ,  Kevin Frankowski

IPC分类号： C07D401/12 ,  C07D209/42 ,  C07D471/04 ,  C07D409/12 ,  C07D235/24 ,  C07D405/12 ,  C07D295/185 ,  C07D213/65 ,  C07D213/81 ,  C07D317/64 ,  C07D307/85 ,  C07D333/70 ,  A61P25/28

摘要： The disclosure of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (I) The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula (I) together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula (I) is administered to the patient together with one or more additional active agents.

公开(公告)号：US20230000857A1

公开(公告)日：2023-01-05

申请号：US17669425

申请日：2022-02-11

申请人： THE JOHNS HOPKINS UNIVERSITY ,  THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human

发明人： Ravit Boger ,  Marc Ferrer ,  Juan Marugan ,  Andres Dulcey Garcia ,  Noel Terrence Southall ,  Xin Hu

IPC分类号： A61K31/4745 ,  A61K31/522 ,  A61K38/05 ,  A61P31/20 ,  A61K45/06 ,  A61P31/22

摘要： The present invention relates to the field of virology. More specifically, the present invention provides methods and compositions useful for prevention and treatment of human cytomegalovirus (CMV). In one embodiment, a pharmaceutical composition comprises (a) emetine or a derivative thereof; (b) a human cytomegalovirus (HCMV) drug; and (c) a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises an adjuvant. In a specific embodiment, the HCMV drug is ganciclovir. In such embodiments, emetine is present at about 1/10 to about 1/100 the normal dosage for amebiasis.

公开(公告)号：US20170001988A1

公开(公告)日：2017-01-05

申请号：US15039781

申请日：2014-11-20

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

发明人： Tsanyang Jake Liang ,  Marc Ferrer ,  Shanshan He ,  Xin Hu ,  Zongyi Hu ,  Juan Jose Marugan ,  Noel Terrence Southall ,  Jingbo Xiao ,  Wei Zheng

IPC分类号： C07D405/10 ,  A61K31/55 ,  A61K45/06 ,  C07D211/58 ,  A61K31/453 ,  A61K31/4468 ,  C07D295/073 ,  A61K31/495 ,  C07D213/16 ,  A61K31/4409 ,  A61K31/4465 ,  C07D211/12 ,  C07D295/03 ,  C07D211/14 ,  C07D403/12 ,  A61K31/496 ,  C07D243/08

CPC分类号： C07D405/10 ,  A61K31/4409 ,  A61K31/4465 ,  A61K31/4468 ,  A61K31/453 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61K45/06 ,  C07D209/48 ,  C07D211/12 ,  C07D211/14 ,  C07D211/58 ,  C07D213/16 ,  C07D243/08 ,  C07D295/03 ,  C07D295/073 ,  C07D295/088 ,  C07D295/096 ,  C07D295/185 ,  C07D403/12

摘要： Disclosed are compounds of formula (I) (formula I), as antiviral agents, antineoplastic agents, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X and Y are independently CH or N, o is 0, 1 or 2, and E is absent or is (CR13R14)m, NH, or S, F is absent or is (CR15R16)n, C=O, or —SO2—, G is absent or is (CR17 CR18)r, H is absent or is C═O, or —SO2- and R1, Ar1, Ar2 are as defined in the specification. These compounds are antiviral agents and are contemplated in the treatment of viral infections, for example, hepatitis C, or are antineoplastic agents.

摘要翻译： 公开了式（I）（式I）的化合物，作为抗病毒剂，抗肿瘤剂，包含这些化合物的药物组合物和这些化合物的使用方法，其中X和Y独立地是CH或N，O是0,1 或（2），E不存在或为（CR 13 R 14）m，NH或S，F不存在或为（CR 15 R 16）n，C = O或-SO 2 - ，G不存在或为（CR 17 CR 18）r ，H不存在或C = O或-SO 2 - ，且R 1，Ar 1，Ar 2如说明书中所定义。 这些化合物是抗病毒剂，并且被考虑用于治疗病毒感染，例如丙型肝炎，或是抗肿瘤剂。

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：US10202367B2

公开(公告)日：2019-02-12

申请号：US15317864

申请日：2015-06-12

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

发明人： Tsanyang Liang ,  Zongyi Hu ,  Juan Jose Marugan ,  Noel Terrence Southall ,  Shanshan He ,  Xin Hu ,  Jingbo Xiao ,  Marc Ferrer ,  Wei Zheng ,  Kevin J. Frankowski ,  Frank J. Schoenen ,  Kelin Li

IPC分类号： C07D413/14 ,  A61K31/4545 ,  C07D417/14 ,  C07D471/08 ,  A61K31/496 ,  A61K31/5377 ,  C07D413/06 ,  A61K31/4178 ,  A61K31/454 ,  A61K31/7056 ,  A61K31/7068 ,  A61K38/07 ,  A61K38/13 ,  A61K38/21

摘要： Disclosed are compounds of formula (I), formula (II), and formula (III): wherein Ar, R1, A, and X are as defined in the specification. These compounds are antiviral agents and are contemplated for use in the treatment of viral infections, for example, hepatitis C. These compounds are also contemplated for use in treating or preventing cancers.

公开(公告)号：US11766423B2

公开(公告)日：2023-09-26

申请号：US16977305

申请日：2019-03-01

申请人： THE JOHNS HOPKINS UNIVERSITY ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, OFFICE OF TECHNOLOGY TRANSFER, NATIONAL INSTITUTES OF HEALTH

发明人： Barbara Slusher ,  Camilo Rojas ,  Ajit G. Thomas ,  Norman Haughey ,  Marc Ferrer ,  Xin Hu

IPC分类号： A61K31/4178 ,  A61P25/28

CPC分类号： A61K31/4178 ,  A61P25/28

摘要： Methods for treating one or more diseases associated with neutral sphingomyelinase 2 (nSMase2) in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of 2,6-dimethoxy-4-(5-phenyl-4-thiophen-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) or a pharmaceutically acceptable salt thereof, are disclosed.

公开(公告)号：US11253511B2

公开(公告)日：2022-02-22

申请号：US16068208

申请日：2017-01-04

申请人： THE JOHNS HOPKINS UNIVERSITY ,  THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services

发明人： Ravit Boger ,  Marc Ferrer ,  Juan Marugan ,  Andres Dulcey Garcia ,  Noel Terrence Southall ,  Xin Hu

IPC分类号： A61K31/4745 ,  A61K31/522 ,  A61P31/22 ,  A61K38/05 ,  A61P31/20 ,  A61K45/06 ,  A61K9/00

摘要： The present invention relates to the field of virology. More specifically, the present invention provides methods and compositions useful for prevention and treatment of human cytomegalovirus (CMV). In one embodiment, a pharmaceutical composition comprises (a) emetine or a derivative thereof; (b) a human cytomegalovirus (HCMV) drug; and (c) a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises an adjuvant. In a specific embodiment, the HCMV drug is ganciclovir. In such embodiments, emetine is present at about 1/10 to about 1/100 the normal dosage for amebiasis.