公开(公告)号：US20230257381A1

公开(公告)日：2023-08-17

申请号：US18005301

申请日：2021-07-15

Applicant: Vanderbilt University ,  H. LUNDBECK A/S

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Alison R. Gregro ,  Kayla J. Temple ,  Madeline F. Long ,  Anna E. Ringuette ,  Logan A. Baker ,  Thomas Jensen

IPC: C07D487/04

CPC classification number: C07D487/04

Abstract: Disclosed herein are analogues of 6-(4-((2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)oxy)piperidin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine, i.e. 7-(4-((phenyl or pyridin-3-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one derivatives of formula (I) 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：US20250017935A1

公开(公告)日：2025-01-16

申请号：US18700120

申请日：2022-10-14

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Julie L. Engers ,  Madeline F. Long ,  Charlotte Park ,  Aaron M. Bender ,  Logan A. Baker

IPC: A61K31/519 ,  A61K31/517 ,  A61P25/18 ,  A61P25/28 ,  C07D471/04 ,  C07D519/00

Abstract: The present invention relates to 7,8-dihydro-5H-1,6-naphthyridine derivatives of formula (I) The present compounds are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) for use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction. An exemplary compound is e.g. example 1: 5,6-dimethyl-4-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]thieno[2,3-d]pyrimidine (compound 1): Data on the activity of exemplary compounds in an mAChR M4 cell-based assay is provided.

公开(公告)号：US12139498B1

公开(公告)日：2024-11-12

申请号：US18639255

申请日：2024-04-18

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  Darren W. Engers ,  Kayla J. Temple ,  Alison R. Gregro ,  Madeline F. Long ,  Anna E. Ringuette ,  Julie L. Engers

IPC: C07D513/04 ,  A61K31/444 ,  A61K31/4985 ,  A61K31/501 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  C07D519/00

Abstract: 6,7-Dihydrothiazolo[5,4-c]pyridines substituted in the 5-position with heterocyclic rings 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：US11884676B2

公开(公告)日：2024-01-30

申请号：US18187868

申请日：2023-03-22

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Alison R. Gregro ,  Kayla J. Temple ,  Madeline F. Long ,  Anna E. Ringuette ,  Logan A. Baker ,  Thomas Jensen

IPC: A61K31/519 ,  C07D487/04

CPC classification number: C07D487/04

Abstract: Disclosed herein are analogues of 6-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1 -yl)-[1,2,4]triazolo[4,3-b]pyridazine of formula (Ib), 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：US20210188820A1

公开(公告)日：2021-06-24

申请号：US16757245

申请日：2018-10-20

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

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：US10736898B2

公开(公告)日：2020-08-11

申请号：US16210495

申请日：2018-12-05

Applicant: Vanderbilt University

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

IPC: A61K31/4365 ,  A61K31/519 ,  A61K31/381 ,  A61P25/28 ,  C07D495/14 ,  A61P25/00

Abstract: Disclosed herein are tricyclic compounds, including thieno[2,3-d:4,5-d′]dipyrimidin-4-amine and pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-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：US20200054643A1

公开(公告)日：2020-02-20

申请号：US16478772

申请日：2018-01-18

Applicant: Vanderbilt University

Inventor： Corey R. Hopkins ,  Charles C. Hong ,  Craig W. Lindsley ,  Darren W. Engers

IPC: A61K31/5377 ,  A61K31/4725 ,  A61K31/437 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/496 ,  A61K31/506 ,  A61K31/519 ,  A61K31/4985

Abstract: The present invention provides small molecule inhibitors of BMP signaling that are useful for treating diseases or conditions associated with BMP signaling, including cancers of the central nervous system.

公开(公告)号：US20190330231A1

公开(公告)日：2019-10-31

申请号：US16347457

申请日：2017-11-07

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Alison R. Gregro ,  Kayla Temple ,  Paul K. Spearing ,  Madeline F. Long ,  Julie L. Engers

IPC: C07D495/14 ,  A61K45/06 ,  A61K31/5025 ,  A61K31/4375 ,  A61K31/5377 ,  A61K31/506 ,  C07D519/00

Abstract: Disclosed herein are thieno[2,3-b:5,4-c′]dipyridin-8-amine and pyrido[4′,3′: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：US10189857B2

公开(公告)日：2019-01-29

申请号：US15703451

申请日：2017-09-13

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Bruce J. Melancon ,  Alison R. Gregro

IPC: C07D495/14 ,  A61K45/06 ,  A61K31/5025 ,  C07B59/00

Abstract: Disclosed herein are substituted 8-aminothieno[3,2-e][1,2,4]triazolo[4,3-b]pyridazine-7-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：US20180179205A1

公开(公告)日：2018-06-28

申请号：US15902547

申请日：2018-02-22

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

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.