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US 2021/0196734 A1Published application
Substituted 6-membered aryl or heteroaryl allosteric modulators of nicotinic acetylcholine receptors
AssigneeMerck Sharp & Dohme Corp.
InventorsBrendan M. Crowley, Ian M. Bell, Andrew John Harvey, Brian T. Campbell, Thomas J. Greshock, Vanessa L. Rada
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Abstract
The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation
Claims17
A compound having the formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is selected from
- Y is 4 substituents, each independently selected from H, (C1-C4)alkyl, halogen, and OH, wherein said alkyl is optionally substituted with one or more halogen or OH;
- A is a 6-membered aryl ring which is substituted with 1 to 4 R groups each independently selected from OH, oxo, amino, amido, carboxyl, keto, cyano, alkoxy, S(O)m-alkyl, halogen, aminoalkyl, hydroxyalkyl, alkyl, cycloalkyl, alkynyl, aryl, heteroaryl, and heterocyclyl, wherein said amino, amido, carboxyl, keto, alkoxy, S(O)m-alkyl, aminoalkyl, hydroxyalkyl, alkyl, cycloalkyl, alkynyl, aryl, heteroaryl and heterocyclyl are optionally substituted with one or more substituents independently selected from halogen, OH, oxo, CF3, OCF3, CN, (C1-C6)alkyl, O(C1-C4)alkyl, S(O)m—(C1-C4)alkyl, C═O(C1-C4)alkyl, (C═O)NR7R8, (C═O)OR7, (C2-C4)alkynyl, (C3-C6)cycloalkyl, O(C3-C6)cycloalkyl, C═O(C3-C6)cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, aryl, heteroaryl and heterocyclyl are optionally independently substituted with one or more halogen, CF3, OH and oxo;
- R1 is H or (C1-C4)alkyl;
- R2 is H or (C1-C4)alkyl;
- R3 is H, halogen, Si(CH3)3 or (C1-C4)alkyl, wherein said alkyl is optionally substituted with one or more halogen;
- R4 is H, halogen or (C1-C4)alkyl, wherein said alkyl is optionally substituted with one or more halogen;
- or, R3 and R4 optionally can come to together to form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring wherein said ring may be optionally substituted with one or more substituents independently selected from OH, halogen, or (C1-C4)alkyl;
- R5 is H or (C1-C4)alkyl;
- R6 is H or (C1-C4)alkyl;
- R7 and R8 are independently selected from H, (C1-C6)alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl are optionally substituted with one or more substituents independently selected from halogen, OH, CF3, (C1-C4)alkyl, O(C1-C4)alkyl, cycloalkyl, CN, aryl, heteroaryl, and heterocyclyl, wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl are optionally substituted with one or more substituents independently selected from halogen, OH, CF3, (C1-C4)alkyl, O(C1-C4)alkyl, CN;
- Ra is H or (C1-C4)alkyl;
- Rb is H or (C1-C4)alkyl;
- and
- m is 0, 1, or 2.
13 more elements
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Dependencies are inferred from the claim text.