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：US20210040074A1

公开(公告)日：2021-02-11

申请号：US16977897

申请日：2019-03-06

申请人： David R. Sibley ,  Kathryn D. Luderman ,  Jennie L. Conroy ,  R. Benjamin Free ,  Prashi Jain ,  Noel T. Southall ,  Marc Ferrer ,  Jeffrey Aubé ,  Kevin Frankowski ,  The United States of America,as represented by the Secretary,Department of Health and Human Service ,  University of Kansas ,  The University of North Carolina at Chapel Hill

发明人： David R. Sibley ,  Kathryn D. Luderman ,  Jennie L. Conroy ,  R. Benjamin Free ,  Prashi Jain ,  Noel T. Southall ,  Marc Ferrer ,  Jeffrey Aubé ,  Kevin Frankowski

IPC分类号： C07D409/12 ,  C07D471/04

摘要： Disclosed are compounds of formulas (I) and (III) for treating or preventing a disease or disorder responsive to activation of a D1 dopamine receptor agonist in a mammal in need thereof, wherein m, n, R1-R6, and R11-R13 are as defined herein. Examples of such disease or disorder include Alzheimer's Disease, schizophrenia, Parkinson's disease, a dyskinesia, and Huntington's disease.

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：US11471460B2

公开(公告)日：2022-10-18

申请号：US16883046

申请日：2020-05-26

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

发明人： Melvin L. DePamphilis ,  Gaurav Sharma ,  Juan Jose Marugan ,  Marc Ferrer ,  Ajit Roy

IPC分类号： A61K31/53 ,  A61P35/00 ,  A61K31/506 ,  C07D239/50 ,  C07D251/54 ,  C07D403/12

摘要： Disclosed is method for treating cancer in a mammal, comprising administering to a mammal in need thereof a compound of the formula: wherein R1, R2, and R3 are as defined herein, wherein the cancer is an autophagy-dependent cancer, in an amount sufficient to induce autophagy in the cell and cause the death of cancer cells. Also disclosed is a method for selectively killing cancer cells in a patient afflicted with cancer, comprising administering to the mammal, wherein the cancer cells are autophagy-dependent cancer cells, in an amount sufficient to induce autophagy in the cells and cause the death of the cancer cells.

公开(公告)号：US20240316056A1

公开(公告)日：2024-09-26

申请号：US18735506

申请日：2024-06-06

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

发明人： Udo Rudloff ,  Serguei Kozlov ,  Juan Jose Marugan ,  Sui Huang ,  Samarjit Patnaik ,  John C. Braisted ,  Noel T. Southall ,  Marc Ferrer ,  Christopher Dextras ,  John Haslam ,  Michael Baltezor

IPC分类号： A61K31/519 ,  A61K31/7068 ,  A61K45/06 ,  A61K47/12 ,  A61P35/04

CPC分类号： A61K31/519 ,  A61K31/7068 ,  A61K45/06 ,  A61K47/12 ,  A61P35/04

摘要： Disclosed are pharmaceutical formulations comprising a compound of formula (I):




in which R1, R2, R3, and R4 are as described herein, or a pharmaceutically acceptable salt thereof. Also provided are methods for treating pancreatic adenocarcinoma comprising administration of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and methods of detecting the change in expression levels of one or both of FoxA1 and FoxO6 in a pancreatic adenocarcinoma tumor sample from a mammal, wherein the mammal has been administered a compound of formula (I), or a pharmaceutically acceptable salt thereof.

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：US20160176831A1

公开(公告)日：2016-06-23

申请号：US14908271

申请日：2014-07-29

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

发明人： Juan Jose Marugan ,  Jingbo Xiao ,  Marc Ferrer ,  Noel Terrence Southall ,  R. Benjamin Free ,  David Robert Sibley

IPC分类号： C07D281/16 ,  C07D417/12

CPC分类号： C07D281/16 ,  C07D417/12

摘要： The disclosure includes compounds and pharmaceutically acceptable salts of Formula (I). Certain compounds and salts of Formula (I) are selective inhibitors of the Dopamine D2 receptor. The variables R1-R4, n, and L are defined herein. The disclosure also provides methods of synthesizing compounds of Formula (I) and pharmaceutical compositions containing compounds of Formula (I). Additionally the disclosure provides methods or treating patients suffering from central nervous system disorders, including Tourette's syndrome, bipolar disorder, hyperprolactinemia, tardive dyskinesia, Huntington's chorea, psychosis, depression, or schizophrenia.

摘要翻译： 本公开内容包括式（I）的化合物和药学上可接受的盐。 某些化合物和式（I）的盐是多巴胺D2受体的选择性抑制剂。 变量R1-R4，n和L在本文中定义。 本公开还提供了合成式（I）化合物和含有式（I）化合物的药物组合物的方法。 此外，本公开提供方法或治疗患有中枢神经系统疾病的患者，包括图雷特综合征，双相情感障碍，高催乳素血症，迟发性运动障碍，亨廷顿氏舞蹈病，精神病，抑郁症或精神分裂症。

公开(公告)号：US11241436B2

公开(公告)日：2022-02-08

申请号：US16480885

申请日：2018-01-25

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

发明人： Congcong He ,  Sui Huang ,  Chen Wang ,  Altea Rocchi ,  Juan Jose Marugan ,  Marc Ferrer ,  Samarjit Patnaik ,  Yuchi Chen ,  Kevin Frankowski ,  Frank J. Schoenen

IPC分类号： A61K31/519 ,  A61P25/30 ,  A61K31/704

摘要： The invention provides a compound of formula (I): wherein R1, R2, R3, and R4 are as defined herein, ginsenoside Rg2 of structure (II): or a combination thereof, for use in treating or preventing a condition responsive to the induction of autophagy in a brain of a mammal in need thereof.