Substituted 2-(4-heterocyclylbenzyl)isoindolin-1-one analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M1
In one aspect, the invention relates to substituted 2-(4-heterocyclylbenzyl)isoindolin-1-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 1 (mAChR M 1 ); synthesis methods for 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. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
1. A compound having a structure represented by a formula:
wherein each of R 1a , R 1b , and R 1c is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy-C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, and C1-C6 dialkylamino;
wherein each of R 2a , R 2b , R 2c , and R 2d is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy-C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, and C1-C6 dialkylamino;
wherein each of R 5a , R 5b , R 5c , and R 5d is independently selected from hydrogen, halogen, hydroxyl, cyano, —NH 2 , C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkylamino, and C1-C6 dialkylamino, provided that at least one of R 5a , R 5b , R 5c , and R 5d is hydrogen; and
wherein R 6 is selected from hydrogen and C1-C6 alkyl,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , having a structure represented by a formula:
3. The compound of claim 1 , having a structure represented by a formula:
4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
5. A kit comprising at least one compound having a structure represented by a formula:
wherein each of R 1a , R 1b , and R 1c is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy-C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, and C1-C6 dialkylamino;
wherein each of R 2a , R 2b , R 2c , and R 2d is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy-C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, and C1-C6 dialkylamino;
wherein each of R 5a , R 5b , R 5c , and R 5d is independently selected from hydrogen, halogen, hydroxyl, cyano, —NH 2 , C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkylamino, and C1-C6 dialkylamino, provided that at least one of R 5a , R 5b , R 5c , and R 5d is hydrogen; and
wherein R 6 is selected from hydrogen and C1-C6 alkyl,
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , having a structure represented by formula:
wherein each of R 2a and R 2d is independently selected from hydrogen and halogen; and
wherein R 6 is selected from hydrogen and methyl.
7. The compound of claim 1 , having a structure represented by formula:
wherein each of R 2a and R 2d is independently selected from hydrogen and halogen; and
wherein R 6 is selected from hydrogen and methyl.
8. The compound of claim 1 , having a structure represented by formula:
9. The compound of claim 1 , having a structure represented by formula:
10. The compound of claim 1 , having a structure represented by formula: