公开(公告)号：US20200323857A1

公开(公告)日：2020-10-15

申请号：US16769684

申请日：2018-12-05

Applicant: Vanderbilt University

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

IPC: A61K31/519 ,  A61K45/06 ,  C07D495/14 ,  C07D519/00

Abstract: Disclosed herein are tricyclic compounds, including 3-(difluoromethyl)-4-methylpyrimido[4′,5′:4,5]thieno[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators 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 neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

公开(公告)号：US20200079756A1

公开(公告)日：2020-03-12

申请号：US16469972

申请日：2017-12-15

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Julie L. Engers ,  Madeline F. Long

IPC: C07D401/14 ,  C07D237/28 ,  C07D403/14 ,  C07D403/12 ,  A61P25/28

Abstract: Disclosed herein are 2,4-dimethylquinoline-6-carboxamide compounds and 3,4-dimethylcinnoline-6-carboxamide compounds, which may be useful as positive allosteric modulators 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 neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

公开(公告)号：US20200024275A1

公开(公告)日：2020-01-23

申请号：US16337977

申请日：2017-08-16

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Katrina A. Bollinger ,  Darren W. Engers ,  Anna L. Blobaum ,  Julie L. Engers ,  Jerri M. Rook

IPC: 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.

公开(公告)号：US20190330226A1

公开(公告)日：2019-10-31

申请号：US16395765

申请日：2019-04-26

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Paul K. Spearing ,  Aaron M. Bender

IPC: C07D495/04 ,  C07D487/04 ,  C07D513/04

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.

公开(公告)号：US10227343B2

公开(公告)日：2019-03-12

申请号：US15547775

申请日：2016-02-01

Applicant: Vanderbilt University

Inventor： P. Jeffrey Conn ,  Craig W. Lindsley ,  Colleen M. Niswender ,  Corey R. Hopkins ,  Joanne Bronson ,  Yong-Jin Wu ,  Kyle Emmitte ,  Joe Panarese ,  Darren W. Engers ,  Julie Engers

IPC: C07D471/04 ,  A61K31/496 ,  A61K31/437 ,  A61K31/554 ,  A61K31/553 ,  C07D487/04 ,  A61K31/4985 ,  A61K31/4725 ,  A61K31/541 ,  A61K31/4745 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/502 ,  C07D401/12 ,  A61K31/4375 ,  C07D519/00 ,  A61K31/519 ,  A61K45/06

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

公开(公告)号：US20170369505A1

公开(公告)日：2017-12-28

申请号：US15630200

申请日：2017-06-22

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Sean Bollinger ,  James C. Tarr ,  Paul Spearing ,  Julie L. Engers ,  Madeline Long ,  Thomas M. Bridges

IPC: C07D495/14 ,  C07D519/00 ,  C07D493/14

CPC classification number: C07D495/14 ,  C07D493/14 ,  C07D519/00

Abstract: Disclosed herein are tricyclic compounds, including pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3′,2′:4,5]furo[3, 2-d]pyrimidin-4-amine, and pyrimido[4′,5′:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators 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 neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

公开(公告)号：US09586964B2

公开(公告)日：2017-03-07

申请号：US14354560

申请日：2012-10-28

Applicant: Vanderbilt University

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

IPC: C07D519/00 ,  C07D403/10 ,  C07D487/04 ,  C07D401/10 ,  C07D401/14 ,  C07D471/04 ,  C07D417/10 ,  C07D405/10 ,  C07D275/06

CPC classification number: C07D471/04 ,  C07D275/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/10 ,  C07D417/10 ,  C07D487/04 ,  C07D519/00

Abstract: In one aspect, the invention relates to substituted 2-(4-heterocyclylbenzyl)isoindolin-1-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，本发明涉及用作毒蕈碱乙酰胆碱受体M1（mAChR M1）的正变构调节剂的取代的2-（4-杂环基苄基）异二氢吲哚-1-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，而不是限制本发明。

公开(公告)号：US20250136600A1

公开(公告)日：2025-05-01

申请号：US19002368

申请日：2024-12-26

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  Darren W. Engers ,  Kayla J. Temple ,  Alison R. Gregro ,  Alexa E. Richardson ,  Madeline F. Long

IPC: C07D471/04 ,  A61K31/4545 ,  C07B59/00

Abstract: Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

公开(公告)号：US20250122200A1

公开(公告)日：2025-04-17

申请号：US19002334

申请日：2024-12-26

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  Darren W. Engers ,  Kayla J. Temple ,  Alison R. Gregro ,  Alexa E. Richardson ,  Madeline F. Long

IPC: C07D471/04 ,  A61K31/4545 ,  C07B59/00

Abstract: Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

公开(公告)号：US20250101041A1

公开(公告)日：2025-03-27

申请号：US18729768

申请日：2023-01-19

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Kayla J. Temple ,  Alison R. Gregro ,  Madeline F. Long ,  Logan A. Baker ,  Aaron M. Bender ,  Anna E. Ringuette ,  Sara L. Biscotto

IPC: C07D519/00 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/5383 ,  C07D487/04

Abstract: 5,6,7,8-Tetrahydro-1,6-naphthyridines substituted in the 6-position with pyrimido[1,2-b]pyridazin-4-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.