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US 12,600,726 B2Granted
Antagonists of the muscarinic acetylcholine receptor M4
AssigneeVanderbilt University
InventorsCraig W. Lindsley, Thomas M. Bridges, P. Jeffrey Conn, Aaron M. Bender, Darren W. Engers
Life of this patent
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Abstract
Disclosed herein are cyclopropylpiperidine compounds, which may be useful as antagonists of the muscarinic acetylcholine receptor M4 (niAChR 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.
Claims15
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- A is a thiazol-2,5-diyl, pyridazin-3,6-diyl, pyrazin-2,5-diyl, pyridin-2,5-diyl, or phthalazin-1,4-diyl, wherein A is optionally substituted with 1-4 substituents independently selected from halo, C1-C4 alkyl, and C1-C4 haloalkyl;
- Q is selected from NRa, O, and CRbRc;
- R1 is selected from —CH═CH—C1-C4 alkyl, —CH═CH-G, C5-C8cycloalkenyl, a 4- to 8-membered monocyclic heterocyclyl, a 6- to 12-membered aryl, and a 5- to 6-membered monocyclic heteroaryl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
- wherein the cycloalkenyl, heterocyclyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, cyano, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NHCOR′;
- G is a 6- to 12-membered aryl optionally substituted with 1, 2, or 3 substituents independently selected from C1-C4 alkyl, halo, cyano, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and —NHCOR′;
- R′, at each occurrence, is independently C1-C4 alkyl:
- R2 and R3 are independently selected from hydrogen, C1-C4 alkyl, and halo, or R2 and R3 are taken together to form an oxo group;
- R6 is selected from C1-C8 alkyl and —(CRfRg)n—Y1;
- Rf is hydrogen:
- Rg is selected from hydrogen, C1-C4 alkyl and phenyl:
- Y1 is selected from:
- C3-C10-cycloalkyl;
- C5-C10-cycloalkenyl;
- phenyl;
- a 5- to 6-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from N, O and S;
- and a 5- to 8-membered heterocyclyl having 1 or 2 heteroatoms independently selected from N, O and S;
- wherein the cycloalkyl, cycloalkenyl, phenyl, heteroaryl and heterocyclyl are unsubstituted or substituted with 1 or 2 substituents independently selected from C1-C4 alkyl, halo, and C1-C4 haloalkyl;
- each Ra, Rb, and Rc is independently selected from hydrogen and C1-C4 alkyl;
- m is 0;
- and
- n is 0 or 1.
19 more elements
Dependencies are inferred from the claim text.