公开(公告)号：US20250026752A1

公开(公告)日：2025-01-23

申请号：US18700130

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 ,  Logan A. Baker ,  Rory A. Capstick ,  Charlotte Park ,  Andrew S. Felts ,  Kayla J. Temple ,  Aaron M. Bender

IPC: C07D471/04 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/538 ,  A61K31/5383 ,  C07D519/00

Abstract: Disclosed herein are analogs of 4-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)quinazoline and 4-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)pyrido[2,3-d]pyrimidine, 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：US20250002507A1

公开(公告)日：2025-01-02

申请号：US18700101

申请日：2022-10-14

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Darren W. Engers ,  Alison R. Gregro ,  Katrina A. Bollinger ,  Charlotte Park ,  Kayla J. Temple ,  Logan A. Baker ,  Madeline F. Long ,  Anna E. Ringuette ,  Julie L. Engers

IPC: C07D519/00 ,  A61K31/5025

Abstract: The present invention relates to 6-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-7,8-dihydro-5H-1,6-naphthyridine derivatives, 6-(imidazo[1,2-b]pyridazin-6-yl)-7,8-dihydro-5H-1,6-naphthyridine derivatives or 6-(imidazo[1,5-b]pyridazin-6-yl)-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. compound 1 Data on the activity of exemplary compounds in an mAChR M4 cell-based assay is provided. wherein: Z1 is CR1; Z2 is CR2; Z3 is CR3; Z4 is N; R1 is hydrogen, C1-4alkyl, or OC1-4alkyl; R2 is G2, R, C1-6alkyl, halogen, C1-6haloalkyl, —ORb, -L-ORb, -L-R, -L-G2, -L(OH)-G2, or hydrogen; R3 is hydrogen; 1
6-(7,8-dimethyl- [1,2,4]triazolo[4,3- b]pyridazin-6-yl)- 7,8-dihydro- 5H-1,6-naphthyridine

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：US20240140943A1

公开(公告)日：2024-05-02

申请号：US18263052

申请日：2022-01-26

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Changho Han ,  Jinming Li, I

IPC: C07D471/04 ,  A61P25/00

CPC classification number: C07D471/04 ,  A61P25/00

Abstract: Arylsulfonamides of 4-heteroaryl-cyclohexyls, and their derivatives, are competitive and non-competitive inhibitors of the muscarinic acetylcholine receptor M5 (mAChR M5) and have utility in the treatment of psychiatric disorders such as substance-related misuse, substance-related disorder relapse, anxiety, depression, and psychosis.

公开(公告)号：US20240116902A1

公开(公告)日：2024-04-11

申请号：US18486712

申请日：2023-10-13

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：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.

公开(公告)号：US20230150986A1

公开(公告)日：2023-05-18

申请号：US17784365

申请日：2020-12-10

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  P. Jeffrey Conn ,  Aaron M. Bender ,  Katrina A. Bollinger ,  Trever R. Carter ,  Jerri M. Rook ,  Jonathan W. Dickerson ,  Julie L. Engers ,  Kayla J. Temple ,  Changho Han ,  Matthew Spock ,  Logan A. Baker ,  Thomas M. Bridges

IPC: C07D405/14 ,  C07D401/14 ,  C07D403/12 ,  C07D498/04 ,  C07D409/14

CPC classification number: C07D405/14 ,  C07D401/14 ,  C07D403/12 ,  C07D498/04 ,  C07D409/14 ,  C07B2200/05 ,  C07B2200/09

Abstract: Disclosed herein are 2,3,5-trifluorophenyl-pyridazine substituted hexahydro-1H-cyclopenta[c]pyrrole 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：US11427573B2

公开(公告)日：2022-08-30

申请号：US16639539

申请日：2018-08-16

Applicant: Vanderbilt University

Inventor： P. Jeffrey Conn ,  Craig W. Lindsley ,  Andrew S. Felts ,  Colleen M. Niswender ,  Rory A. Capstick ,  Paul K. Spearing ,  Sean R. Bollinger

IPC: C07D405/14 ,  C07D407/14 ,  A61P25/00 ,  C07D409/14 ,  C07D519/00 ,  C07D401/12 ,  C07D471/04

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

公开(公告)号：US11414406B2

公开(公告)日：2022-08-16

申请号：US16966306

申请日：2019-02-01

Applicant: Vanderbilt University

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

IPC: C07D403/14 ,  C07D403/12 ,  C07D405/14

Abstract: Disclosed herein are 3-azabicyclo[3.1.0]hexan-6-amine 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.