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：US20230286991A1

公开(公告)日：2023-09-14

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: 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, 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：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：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：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：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：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.