公开(公告)号：US11851428B2

公开(公告)日：2023-12-26

申请号：US17328814

申请日：2021-05-24

申请人： ONO PHARMACEUTICAL CO., LTD. ,  VANDERBILT UNIVERSITY

发明人： Craig W. Lindsley ,  Joshua M. Wieting ,  Kevin M. Mcgowan ,  Jerod S. Denton ,  Kentaro Yashiro ,  Haruto Kurata ,  Yoko Sekioka ,  Takahiro Mori ,  Yuzo Iwaki

IPC分类号： C07D213/36 ,  C07D231/12 ,  C07D249/08 ,  C07D401/04 ,  A61K31/454 ,  C07D471/04 ,  C07C255/57 ,  C07C317/28 ,  C07D209/30 ,  C07D213/89 ,  C07D231/56 ,  C07D235/16 ,  C07D237/24 ,  C07D239/47 ,  C07D249/18 ,  C07D257/04 ,  C07D265/36 ,  C07D271/10 ,  C07D285/14 ,  C07D295/04 ,  C07D513/04

CPC分类号： C07D471/04 ,  C07C255/57 ,  C07C317/28 ,  C07D209/30 ,  C07D213/89 ,  C07D231/56 ,  C07D235/16 ,  C07D237/24 ,  C07D239/47 ,  C07D249/08 ,  C07D249/18 ,  C07D257/04 ,  C07D265/36 ,  C07D271/10 ,  C07D285/14 ,  C07D295/04 ,  C07D401/04 ,  C07D513/04

摘要： Disclosed is a compound of formula (I):






wherein all symbols are defined in the description. Also disclosed are pharmaceutical compositions comprising the compounds, methods of making the compounds, kits comprising the compounds, and methods of using the compounds, compositions and kits for treatment of disorders associated with TREK-1, TREK-2 or both TREK-1 and TREK-2 dysfunction in a mammal.

公开(公告)号：US20240228489A1

公开(公告)日：2024-07-11

申请号：US18554867

申请日：2022-04-14

申请人： Vanderbilt University

发明人： Craig W. Lindsley ,  Darren W. Engers ,  Julie L. Engers ,  Changho Han ,  Alison R. Gregro ,  Madeline F. Long ,  Jinming Li ,  Joseph D. Bungard ,  Cayden J. Dodd

IPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  C07D519/00

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  C07D519/00

摘要： Described are deuterium-labeled 6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one and isoindolin-1-one positive allosteric modulators of muscarinic acetylcholine receptor M1(mAChR M1), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating neurological disorders, psychiatric disorders, or a combination thereof.

公开(公告)号：US20240228468A1

公开(公告)日：2024-07-11

申请号：US18553412

申请日：2022-04-05

申请人： Vanderbilt University

发明人： Aaron M. Bender ,  Matthew Spock ,  Trever R. Carter ,  Melissa A. Korkmaz-Vaisys ,  Logan A. Baker ,  P. Jeffrey Conn ,  Craig W. Lindsley

IPC分类号： C07D403/12 ,  A61K31/351 ,  A61K31/50 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/5377 ,  C07D237/12 ,  C07D237/24 ,  C07D309/06 ,  C07D309/08 ,  C07D401/14 ,  C07D405/14 ,  C07D495/04

CPC分类号： C07D403/12 ,  A61K31/351 ,  A61K31/50 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/5377 ,  C07D237/12 ,  C07D237/24 ,  C07D309/06 ,  C07D309/08 ,  C07D401/14 ,  C07D405/14 ,  C07D495/04

摘要： The present invention relates to (6-((octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl)benzamide (R2b is —C(O)N(RA1)(RA2) and N-(6-((octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl) phenyl) carboxamide (R2b is —N(RB)C(O)RC) derivatives of formula (I) wherein (II) R2b is —C(O)N(RA1)(RA2) or —N(RB)C(O)RC as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4) for the treatment of neurodegenerative disorders, movement disorders or brain disorders, such as e.g. Parkinson's disease, drug-induced Parkinsonism, dystonia, Tourette's syndrome, dyskinesias, schizophrenia, cognitive deficits associated with schizophrenia, excessive daytime sleepiness, attention deficit hyperactivity disorder (ADHD), Huntington's disease, chorea, cerebral palsy, and progressive supranuclear palsy. An exemplary compound is e.g. N-(4-(6-(((3aR,5s,6aS)-2-(2-fluorobenzyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl) phenyl)acetamide (A1) (III).

公开(公告)号：US20240140943A1

公开(公告)日：2024-05-02

申请号：US18263052

申请日：2022-01-26

申请人： Vanderbilt University

发明人： Craig W. Lindsley ,  P. Jeffrey Conn ,  Changho Han ,  Jinming Li, I

IPC分类号： C07D471/04 ,  A61P25/00

CPC分类号： C07D471/04 ,  A61P25/00

摘要： Arylsulfonamides of 4-heteroaryl-cyclohexyls, and their derivatives, are competitive and non-competitive inhibitors of the muscarinic acetylcholine receptor M5 (mAChR M5) and have utility in the treatment of psychiatric disorders such as substance-related misuse, substance-related disorder relapse, anxiety, depression, and psychosis.

公开(公告)号：US20240116902A1

公开(公告)日：2024-04-11

申请号：US18486712

申请日：2023-10-13

申请人： Vanderbilt University

发明人： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Julie L. Engers ,  Kayla J. Temple ,  Aaron M. Bender ,  Logan A. Baker

IPC分类号： C07D403/14 ,  C07D209/52 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D493/08

CPC分类号： C07D403/14 ,  C07D209/52 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D493/08

摘要： Disclosed herein are substituted hexahydro-1H-cyclopenta[c]pyrrole compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

公开(公告)号：US20240109873A1

公开(公告)日：2024-04-04

申请号：US18258351

申请日：2021-12-22

申请人： Vanderbilt University

发明人： Aaron M. Bender ,  Matthew Spock ,  Melissa A. Korkmaz-Vaisys ,  Cori A. Malinky ,  P. Jeffrey Conn ,  Craig W. Lindsley

IPC分类号： C07D405/14

CPC分类号： C07D405/14 ,  C07B2200/05

摘要： Disclosed herein are compounds of formula (III) useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurodegenerative disorders using the compounds and compositions.

公开(公告)号：US20230322799A1

公开(公告)日：2023-10-12

申请号：US18041030

申请日：2021-08-13

申请人： Vanderbilt University

发明人： Aaron M. Bender ,  Matthew Spock ,  P. Jeffrey Conn ,  Craig W. Lindsley

IPC分类号： C07D495/04 ,  C07D405/14 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D495/04 ,  C07D405/14 ,  C07D401/12 ,  C07D401/14 ,  C07B2200/05

摘要： Disclosed herein are 1,2,3,4-tetrahydroisoquinolines and 4, 5, 6, 7-tetrahydrothieno [2, 3-cjpyridines, useful as antagonists of the muscarinic acetylcholine receptor M4 (mA·Ch·RM4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

公开(公告)号：US20230150986A1

公开(公告)日：2023-05-18

申请号：US17784365

申请日：2020-12-10

申请人： Vanderbilt University

发明人： Craig W. Lindsley ,  P. Jeffrey Conn ,  Aaron M. Bender ,  Katrina A. Bollinger ,  Trever R. Carter ,  Jerri M. Rook ,  Jonathan W. Dickerson ,  Julie L. Engers ,  Kayla J. Temple ,  Changho Han ,  Matthew Spock ,  Logan A. Baker ,  Thomas M. Bridges

IPC分类号： C07D405/14 ,  C07D401/14 ,  C07D403/12 ,  C07D498/04 ,  C07D409/14

CPC分类号： C07D405/14 ,  C07D401/14 ,  C07D403/12 ,  C07D498/04 ,  C07D409/14 ,  C07B2200/05 ,  C07B2200/09

摘要： Disclosed herein are 2,3,5-trifluorophenyl-pyridazine substituted hexahydro-1H-cyclopenta[c]pyrrole compounds, useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4) Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.

公开(公告)号：US11427573B2

公开(公告)日：2022-08-30

申请号：US16639539

申请日：2018-08-16

申请人： Vanderbilt University

发明人： P. Jeffrey Conn ,  Craig W. Lindsley ,  Andrew S. Felts ,  Colleen M. Niswender ,  Rory A. Capstick ,  Paul K. Spearing ,  Sean R. Bollinger

IPC分类号： C07D405/14 ,  C07D407/14 ,  A61P25/00 ,  C07D409/14 ,  C07D519/00 ,  C07D401/12 ,  C07D471/04

摘要： Indazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease states associated with glutamate dysfunction.

公开(公告)号：US11414406B2

公开(公告)日：2022-08-16

申请号：US16966306

申请日：2019-02-01

申请人： Vanderbilt University

发明人： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Julie L. Engers ,  Aaron M. Bender

IPC分类号： C07D403/14 ,  C07D403/12 ,  C07D405/14

摘要： Disclosed herein are 3-azabicyclo[3.1.0]hexan-6-amine compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating disorders using the compounds and compositions.