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US 2020/0369666 A1Published application
Antagonists of the muscarinic acetylcholine receptor m4
AssigneeVanderbilt University
InventorsCraig W. Lindsley, P. Jeffrey Conn, Darren W. Engers, Kayla J. Temple
Life of this patent
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Abstract
Disclosed herein are octahydropyrrolo[3,4-b]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.
Claims23
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- A is a five- or six-membered heteroarylene having 1, 2 or 3 heteroatoms independently selected from N, O and S;
- R1 is selected from hydrogen, halo, —ORa, —NRbRc, aryl, and heteroaryl;
- R2 is selected from hydrogen, C1-C4 alkyl, halo, and —ORd;
- R3 is selected from hydrogen and C1-C4 alkyl;
- R4 is selected from C1-C8 alkyl, C1-C8 alkenyl, and —(CReRf)n—Y′;
- each Y′ is independently selected from cycloalkyl, cycloalkenyl, heterocycle, aryl, and heteroaryl;
- each Ra, Rb, Rc, and Rd is independently selected from hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, and aryl;
- each Re is independently selected from hydrogen and C1-C4 alkyl;
- each Rf is independently selected from hydrogen, C1-C4 alkyl, and aryl;
- and
- n is 0, 1, 2, 3, or 4;
- wherein each aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocycle is independently unsubstituted or substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 hydroxyalkyl, hydroxy, cyano, and benzyl.
10 more elements
The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from aryl and heteroaryl, wherein the aryl and heteroaryl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 hydroxyalkyl, hydroxy, cyano, and benzyl. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from phenyl and a 5- or 6-membered heteroaryl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
- and
- the phenyl or heteroaryl is unsubstituted or substituted with 1, 2, or 3 substituents independently selected from halo and C1-C4 alkyl.
1 more element
Dependencies are inferred from the claim text.