公开(公告)号：US20230183219A1

公开(公告)日：2023-06-15

申请号：US17920904

申请日：2021-04-23

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Aaron M. Bender ,  Changho Han ,  Trever R. Carter ,  Matthew Spock

IPC: C07D405/14 ,  C07D403/14 ,  C07D401/14 ,  C07D403/12 ,  C07D493/08 ,  C07D417/14

CPC classification number: C07D405/14 ,  C07D403/14 ,  C07D401/14 ,  C07D403/12 ,  C07D493/08 ,  C07D417/14 ,  C07B2200/05

Abstract: Disclosed herein are substituted hexahydro-1//-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：US20230183218A1

公开(公告)日：2023-06-15

申请号：US17920899

申请日：2021-04-23

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Aaron M. Bender ,  Changho Han

IPC: C07D405/14 ,  C07D403/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D403/14 ,  C07D401/14 ,  C07D487/04

CPC classification number: C07D405/14 ,  C07D403/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D403/14 ,  C07D401/14 ,  C07D487/04

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：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：US20240174655A1

公开(公告)日：2024-05-30

申请号：US18553408

申请日：2022-04-01

Applicant: Vanderbilt University

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

IPC: C07D405/14

CPC classification number: C07D405/14

Abstract: Disclosed herein are (6-(2H-indazol-5-yl)pyridazin-3-yl)octahydrocyclopenta[c]pyrrol-5-amine 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：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：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：US12065433B2

公开(公告)日：2024-08-20

申请号：US17287442

申请日：2019-10-24

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffery Conn ,  Darren W. Engers ,  Aaron M. Bender

IPC: C07D405/14 ,  C07D405/10 ,  C07D413/10 ,  C07D413/14

CPC classification number: C07D405/14 ,  C07D405/10 ,  C07D413/10 ,  C07D413/14 ,  C07B2200/05

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：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.