公开(公告)号：US20150266866A1

公开(公告)日：2015-09-24

申请号：US14664792

申请日：2015-03-20

Applicant: Vanderbilt University

Inventor： P. Jeffrey Conn ,  Craig W. Lindsley ,  Kyle A. Emmitte ,  Andrew S. Felts

IPC: C07D417/14 ,  C07D401/14

CPC classification number: C07D417/14 ,  A61K31/506 ,  C07D401/14 ,  C07D403/14

Abstract: Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. 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.

Abstract translation: 公开了代谢型谷氨酸受体亚型5（mGluR5）的负变构调节剂; 制备化合物的合成方法; 包含该化合物的药物组合物; 以及使用所述化合物和组合物治疗与谷氨酸官能障碍相关的神经和精神障碍的方法。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US20140364409A1

公开(公告)日：2014-12-11

申请号：US13974858

申请日：2013-08-23

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Michael R. Wood ,  James M. Salovich

IPC: C07D495/14

CPC classification number: C07D495/14

Abstract: In one aspect, the invention relates to substituted pyrazolo[3′,4′:4,5]thieno[2,3-c]pyridazine-3-amine analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. 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.

Abstract translation: 一方面，本发明涉及用作正变构调节剂的取代的吡唑并[3'，4'：4,5]噻吩并[2,3-c]哒嗪-3-胺类似物，其衍生物和相关化合物 的毒蕈碱乙酰胆碱受体M4（mAChR M4）; 制备化合物的合成方法; 包含该化合物的药物组合物; 以及使用该化合物和组合物治疗与毒蕈碱性乙酰胆碱受体功能障碍相关的神经和精神疾病的方法。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US20130345203A1

公开(公告)日：2013-12-26

申请号：US13922223

申请日：2013-06-19

Applicant: Vanderbilt University

Inventor： P. Jeffrey Conn ,  Craig W. Lindsley ,  Shaun R. Stauffer ,  José Manuel Bartolomé-Nebreda ,  Susana Conde-Ceide ,  Gregor James Macdonald ,  Han Min Tong ,  Miguel Angel Pena-Piñón ,  Manuel Jesús Alcázar-Vaca ,  José Ignacio Andrés-Gil

IPC: C07D487/04

CPC classification number: A61K31/4985 ,  A61K31/506 ,  A61K31/551 ,  C07D487/04

Abstract: In one aspect, the invention relates to substituted bicyclic alkoxy pyrazole analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. 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：US20130178458A1

公开(公告)日：2013-07-11

申请号：US13692969

申请日：2012-12-03

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Michael R. Wood ,  Bruce J. Melancon ,  Yiu-Yin Cheung

IPC: C07D401/14 ,  C07D405/14 ,  C07D498/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D413/14

CPC classification number: C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

Abstract: In one aspect, the invention relates to substituted (1-(methylsulfonyl)azetidin-3-yl)(heterocycloalkyl)methanone analogs, derivatives thereof, and related compounds, which are useful as antagonists of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. 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.

Abstract translation: 一方面，本发明涉及可用作毒蕈碱性乙酰胆碱受体M1（mAChR M1）的拮抗剂的取代的（1-（甲基磺酰基）氮杂环丁烷-3-基）（杂环烷基）甲酮类似物，其衍生物和相关化合物。 制备化合物的合成方法; 包含该化合物的药物组合物; 以及使用该化合物和组合物治疗与毒蕈碱性乙酰胆碱受体功能障碍相关的神经和精神疾病的方法。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US20130123236A1

公开(公告)日：2013-05-16

申请号：US13674016

申请日：2012-11-10

Applicant: VANDERBILT UNIVERSITY

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Michael R. Wood ,  Corey R. Hopkins ,  Bruce J. Melancon ,  Michael S. Poslusney

IPC: C07D487/10 ,  C07D491/113 ,  C07D491/107 ,  C07D471/10

CPC classification number: C07D487/10 ,  C07D471/10 ,  C07D491/107 ,  C07D491/113

Abstract: In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. 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.

Abstract translation: 一方面，本发明涉及可用作毒蕈碱性乙酰胆碱受体M1（mAChR M1）的正变构调节剂的取代的苄基螺二氢吲哚-2-酮类似物化合物，其衍生物和相关化合物。 制备化合物的合成方法; 包含该化合物的药物组合物; 以及使用该化合物和组合物治疗与毒蕈碱性乙酰胆碱受体功能障碍相关的神经和精神疾病的方法。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US20240287050A1

公开(公告)日：2024-08-29

申请号：US18567212

申请日：2022-06-10

Applicant: Vanderbilt University

Inventor： Aaron M. Bender ,  Changho Han ,  Matthew Spock ,  Cori A. Malinky ,  Craig W. Lindsley ,  P. Jeffrey Conn

IPC: C07D405/14 ,  A61K31/501 ,  C07D401/14 ,  C07D403/12

CPC classification number: C07D405/14 ,  A61K31/501 ,  C07D401/14 ,  C07D403/12

Abstract: Disclosed are compounds of formula (I) wherein G1 is as antagonists of the muscarinic acetylcholine receptor M4 (mAChR M4) for use in the treatment of e.g. a neurodegenerative disorder, a movement disorder, or a brain disorder, 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. (2,5-difluoro-4-(6-(((3aR,5s,6aS)-2- ((tetrahydro-2H-pyran-4-yl)methyl)octahydrocyclopenta[c]pyrrol-5- yl)amino)pyridazin-3-yl)phenyl)(imino)(methyl)-λ6-sulfanone (e.g. example 12; compound no. 7) Pharmacological data on the activity of the compounds in an mAChR M4 cell-based assay are provided (e.g. table 2)










TABLE 2









Human M4










Cpd. No.
IC50 (nM)
Emin (%)*












1
13.4
4


2
39.6
2


3
18.5
3


4
584
6


5
75.4
3


6
188
3


7
46.0
3


8
560
7


9
18.4
3


10
1.8
2


11
86.2
3


12
43.4
2


13
8.6
3





*% ACh maximum at 30 μM.

公开(公告)号：US20240083907A1

公开(公告)日：2024-03-14

申请号：US17766341

申请日：2020-10-02

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Aaron M. Bender ,  Matthew Spock ,  Changho Han

IPC: C07D495/04 ,  C07B59/00 ,  C07D405/14

CPC classification number: C07D495/04 ,  C07B59/002 ,  C07D405/14 ,  C07B2200/05

Abstract: 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：US11820757B2

公开(公告)日：2023-11-21

申请号：US17688709

申请日：2022-03-07

Applicant: Vanderbilt University

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

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

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

Abstract: 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：US20230122344A1

公开(公告)日：2023-04-20

申请号：US17784356

申请日：2020-12-10

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Aaron M. Bender ,  Matthew Spock ,  Changho Han

IPC: C07D405/14 ,  C07D403/14

Abstract: 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：US11111251B2

公开(公告)日：2021-09-07

申请号：US15998899

申请日：2017-02-16

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Katrina A. Bollinger ,  Julie L. Engers

IPC: C07D413/14 ,  C07D403/14 ,  C07D471/04 ,  C07D495/04

Abstract: Described are 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.