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：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：US20250026743A1

公开(公告)日：2025-01-23

申请号：US18691617

申请日：2022-09-14

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  Kayla J. Temple ,  Katherine E. Crocker ,  Aaron M. Bender ,  Jackson P. Waters ,  Matthew Spock ,  Cori A. Malinky ,  Cayden J. Dodd

IPC: C07D413/14 ,  A61K31/4439 ,  A61K31/444 ,  C07D401/14 ,  C07D417/14

Abstract: Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGlu5); 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：US20240010640A1

公开(公告)日：2024-01-11

申请号：US18253094

申请日：2021-11-18

Applicant: Vanderbilt University

Inventor： Aaron M. Bender ,  Matthew Spock ,  Melissa A. Korkmaz-Vaisys ,  Craig W. Lindsley ,  P. Jeffrey Conn

IPC: C07D405/14 ,  C07D401/14

CPC classification number: C07D405/14 ,  C07D401/14

Abstract: Disclosed herein are 6-((octahydrocyclopenta[c]pyrrol-5-yl)amino)pyridazin-3-yl-substituted pyridinones, pyrimidinones, and pyridazinones, 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：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：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：US20240228468A1

公开(公告)日：2024-07-11

申请号：US18553412

申请日：2022-04-05

Applicant: Vanderbilt University

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

IPC: 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 classification number: 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

Abstract: 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：US20240109873A1

公开(公告)日：2024-04-04

申请号：US18258351

申请日：2021-12-22

Applicant: Vanderbilt University

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

IPC: C07D405/14

CPC classification number: C07D405/14 ,  C07B2200/05

Abstract: 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

Applicant: Vanderbilt University

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

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

CPC classification number: C07D495/04 ,  C07D405/14 ,  C07D401/12 ,  C07D401/14 ,  C07B2200/05

Abstract: 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.