公开(公告)号：US11999716B2

公开(公告)日：2024-06-04

申请号：US17287492

申请日：2019-10-24

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Joseph R. Alvarado ,  Jianhua Tian ,  Kenneth M. Meyers ,  Changho Han ,  Jonathan J. Mills ,  Kevin B. Teuscher ,  Shaun R. Stauffer ,  Stephen W. Fesik ,  Rocco D. Gogliotti

IPC: C07D401/14 ,  C07D217/16 ,  C07D401/06 ,  C07D405/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14 ,  C07D487/04

CPC classification number: C07D401/14 ,  C07D217/16 ,  C07D401/06 ,  C07D405/14 ,  C07D413/06 ,  C07D413/14 ,  C07D417/06 ,  C07D417/14 ,  C07D487/04

Abstract: Isoquinolinone compounds and derivatives inhibit WDR5 and associated protein-protein interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

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：US20230012362A1

公开(公告)日：2023-01-12

申请号：US17287492

申请日：2019-10-24

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Joseph R. Alvarado ,  Jianhua Tian ,  Kenneth M. Meyers ,  Changho Han ,  Jonathan J. Mills ,  Kevin B. Teuscher ,  Shaun R. Stauffer ,  Stephen W. Fesik

IPC: C07D401/14 ,  C07D401/06 ,  C07D487/04 ,  C07D405/14 ,  C07D417/14 ,  C07D417/06 ,  C07D413/14 ,  C07D217/16 ,  C07D413/06

Abstract: Isoquinolinone compounds and derivatives inhibit WDRS and associated protein-protein interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

公开(公告)号：US20220289673A1

公开(公告)日：2022-09-15

申请号：US17631114

申请日：2020-07-29

Applicant: Vanderbilt University

Inventor： William P. Tansey ,  Stephen W. Fesik ,  Shaun R. Stauffer ,  Alex G. Waterson ,  Changho Han ,  Joseph R. Alvarado ,  Jonathan D. MacDonald ,  Selena Chacon Simon ,  Sameer S. Nikhar ,  Alexey Kuznetsov

IPC: C07C311/21 ,  C07C311/29 ,  C07C311/39 ,  C07C311/43 ,  C07C317/34 ,  C07C317/38 ,  C07C317/48 ,  C07C323/49 ,  C07C381/00 ,  C07D205/04 ,  C07D207/08 ,  C07D207/12 ,  C07D211/48 ,  C07D207/27 ,  C07D213/40 ,  C07D213/56 ,  C07D213/64 ,  C07D215/36 ,  C07D233/36 ,  C07D239/26 ,  C07D249/14 ,  C07D265/30 ,  C07D241/04 ,  C07D305/08 ,  C07D307/14 ,  C07D307/18 ,  C07D307/22 ,  C07D307/52 ,  C07D307/79 ,  C07D309/04 ,  C07D309/10 ,  C07D309/14 ,  C07D309/22 ,  C07D333/20 ,  C07D333/24

Abstract: Substituted N-phenyl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

公开(公告)号：US20220242849A1

公开(公告)日：2022-08-04

申请号：US17613717

申请日：2020-06-04

Applicant: Vanderbilt University

Inventor： Taekyu Lee ,  Changho Han ,  Jonathan J. Mills ,  Kevin B. Teuscher ,  Jianhua Tian ,  Kenneth M. Meyers ,  Somenath Chowdhury ,  Stephen W. Fesik

IPC: C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

Abstract: Quinazolin-4(3H)-one, 2,3-dihydroquinazolin-4(1H)-one, 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one, and 3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione compounds and derivatives inhibit WDR5 and associated protein-protein interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

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：US10221175B2

公开(公告)日：2019-03-05

申请号：US15568936

申请日：2016-04-22

Applicant: Vanderbilt University

Inventor： P. Jeffrey Conn ,  Craig W. Lindsley ,  Kyle A. Emmitte ,  Changho Han ,  Julie L. Engers ,  Aaron M. Bender

IPC: A61K31/395 ,  C07D471/14 ,  A61K31/506 ,  A61K31/513 ,  A61K31/517 ,  A61K31/519 ,  A61P25/28 ,  A61P25/00

Abstract: Substituted pyrrolopyridine, imidazopyridine and triazolopyridine compounds having a formula are positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1) and the compounds and their pharmaceutical compositions may be useful in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction. Compounds of the invention may be prepared in several steps from 2-halo-5,6-dihydro-7H-pyrrolo[3,4-b]pyridin-7-one intermediates.

公开(公告)号：US20240228489A1

公开(公告)日：2024-07-11

申请号：US18554867

申请日：2022-04-14

Applicant: Vanderbilt University

Inventor： Craig W. Lindsley ,  Darren W. Engers ,  Julie L. Engers ,  Changho Han ,  Alison R. Gregro ,  Madeline F. Long ,  Jinming Li ,  Joseph D. Bungard ,  Cayden J. Dodd

IPC: C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  C07D519/00

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  C07D519/00

Abstract: Described are deuterium-labeled 6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one and isoindolin-1-one 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.