IP Library › Granted Patent US 11,472,810

Granted Patent B2

US 11,472,810 · App. 17/079,951 · Granted Oct 18, 2022

Imidazopyrazinones as PDE1 inhibitors

Inventors: Jan Kehler (Lyngby, DK); Lars Kyhn Rasmussen (Vanløse, DK); Morten Langgård (Glostrup, DK); Mikkel Jessing (Frederiksberg, DK); Karsten Juhl (Greve, DK); Paulo Jorge Vieira Vital (Copenhagen, DK)

Assignee: H. Lundbeck A/S

C07D487/04 C07D519/00

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Quick Facts

Patent No.: US 11,472,810
App. No.: 17/079,951
Granted: Oct 18, 2022
Kind: B2

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Abstract

The present invention provides imidazopyrazinones as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

Claims (172)

1. A method for the treatment of a neurodegenerative disorder, selected from the group consisting of Alzheimer's Disease, Parkinson's Disease and Huntington's Disease, or for the treatment of a psychiatric disorder selected from the group consisting of Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or for the treatment of restless leg syndrome, wherein said method comprises administering to a subject in need thereof a therapeutically effective amount of a compound or formula (I), or pharmaceutically acceptable salt thereof:

wherein

n is 0 or 1;

q is 0 or 1;

R1 is selected from the group consisting of benzyl, indanyl, indoline and 5-membered heteroaryls; all of which can be substituted with a substituent selected from the group consisting of halogen and C 1 -C 3 alkyl; or

R1 is selected from the group consisting of saturated monocyclic rings containing 4-6 carbon atoms and 1-2 nitrogen atoms; all of which can be substituted one or more times with one or more substituents selected from the group consisting of methyl, fluorine and sulfonamide; or

R1 is selected from the group consisting of lactams containing 4-6 carbon atoms; all of which can be substituted one or more times with one or more substituents selected from the group consisting of methyl and fluorine; or

R1 is is a bicyclic ethers such as, which can be substituted one or more times with one or more substituents selected from the group consisting of methyl and fluorine; or

R1 is selected from the group consisting of linear or branched C 1 -C 8 alkyl, saturated monocyclic C 3 -C 8 cycloalkyl, oxetanyl, tetrahydrofuranyl and tetrathydropyranyl; all of which can be substituted one or more times with one or more substituents selected from the group consisting of methyl, fluorine, hydroxy, cyano or methoxy; or

R1 is a linear or branched C 1 -C 3 alkyl, which is substituted with a substituent selected from phenyl and 5-membered heteroaryl, wherein said 5-membered heteroaryl can be substituted with one or more C 1 -C 3 alkyls; or

R1 is selected from the group consisting of morpholine, tetrahydrofuran-3-amine, hexahydro-2H-furo[3,2-b]pyrrole and homomorpholine; all of which can be substituted with one or more substituents selected from the group consisting of C 1 -C 3 alkyl;

R2 is selected from the group consisting of hydrogen, linear or branched C 1 -C 8 alkyl, phenyl, saturated monocyclic C 3 -C 8 cycloalkyl, oxetanyl, benzo[d][1,3]dioxolyl, tetrahydrofuranyl and tetrahydropyranyl; or

R2 is phenyl or pyridyl substituted with one or more substituents selected from the group consisting of hydroxyl, amino, cyano, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 3 -C 5 cycloalkoxy, C 3 -C 5 cycloalkyl-methoxy, C 1 -C 3 fluoroalkoxy, and —NC(O)CH 3 ; or

R2 is a 5-membered heteroaryl which can be substituted with one or more C 1 -C 3 alkyl;

R3 is selected from the group consisting of hydrogen, halogen, C 1 -C 5 alkyl, C 3 -C 5 cycloalkyl and phenyl; or

R3 is selected from the group consisting of phenyl substituted one or more times with C 1 -C 3 alkyl; methyl substituted one, two or three times with fluorine; ethyl substituted one, two or three times with fluorine;

R4 is hydrogen;

with the proviso that R2 and R3 cannot be hydrogen at the same time;

with the proviso that the compound of formula (I) is not one of the three following compounds:

3-methyl-7-(4-(trifluoromethoxy)benzyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-butyl-3-methylimidazo[1,5-a]pyrazin-8(7H)-one; and

7-(4-methoxybenzyl)-3-methylimidazo[1,5-a]pyrazin-8(7H)-one.

2. The method of claim 1 , wherein:

R1 is selected from the group consisting of linear or branched C 1 -C 8 alkyl, saturated monocyclic C 3 -C 8 cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl;

R2 is selected from the group consisting of linear or branched C 1 -C 8 alkyl, phenyl, and saturated monocyclic C 3 -C 8 cycloalkyl; or

R2 is selected from the group consisting of phenyl substituted with a substituent selected from the group consisting of halogen, C 1 -C 3 alkyl and methoxy;

R3 is selected from the group consisting of hydrogen, C 1 -C 3 alkyl, and halogen; and

R4 is hydrogen.

3. The method of claim 1 , wherein R1 is C 1 -C 3 alkyl.

4. The method of claim 1 , wherein R1 is selected from tetrahydrofuranyl and tetrahydropyranyl.

5. The method of claim 1 , wherein R1 is C 3 -C 5 cycloalkyl.

6. The method of claim 1 , wherein R2 is C 1 -C 3 alkyl.

7. The method of claim 1 , wherein R2 is phenyl.

8. The method of claim 1 , wherein R2 is phenyl substituted with a substituent selected from the group consisting of fluorine, chlorine, methyl and methoxy.

9. The method of claim 1 , wherein R2 is saturated monocyclic C 5 -C 7 cycloalkyl.

10. The method of claim 1 , wherein R3 is selected from hydrogen, methyl, and bromine.

11. The method of claim 1 , wherein R3 is selected from hydrogen and methyl; and

wherein R2 is selected from the group consisting of linear or branched C 1 -C 8 alkyl, phenyl, saturated monocyclic C 3 -C 8 cycloalkyl, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl;

R2 is phenyl or pyridyl substituted with one or more substituents selected from the group consisting of hydroxyl, amino, cyano, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 fluoroalkoxy, and —NC(O)CH 3 ; or

R2 is a 5-membered heteroaryl which can be substituted with C 1 -C 3 alkyl.

12. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is selected from the group consisting of:

7-(3-Fluorobenzyl)-3-propylimidazo[1,5-a]pyrazin-8(7H)-one;

6-Benzyl-7-(3-fluorobenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-Benzyl-7-(cyclohexylmethyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cyclohexylmethyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-Fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-Cyclopropyl-7-(3-fluorobenzyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cyclopentylmethyl)-3-cyclopropylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cyclohexylmethyl)-3-cyclopropylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-Fluorobenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cyclopentylmethyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cyclohexylmethyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cycloheptylmethyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(Cycloheptylmethyl)-3-cyclopropylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-Chlorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-Bromo-7-(3-fluorobenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-Benzyl-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(2-Fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-Chlorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(2-Chlorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-Methoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-Methyl-7-(2-methylbenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-Methyl-7-(4-methylbenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-Methoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one,

7-(4-Fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-Methyl-7-(3-methylbenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-(4-methyltetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

4-(7-(3-fluorobenzyl)-6-methyl-8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-3-yl)tetrahydro-2H-pyran-4-carbonitrile;

7-(3-fluorobenzyl)-3-(4-methoxytetrahydro-2H-pyran-4-yl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-(4-fluorotetrahydro-2H-pyran-4-yl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-2-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-2-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(3-fluorobenzyl)-6-methyl-3-(3-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(3-fluorobenzyl)-6-methyl-3-(3-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-(1-methylcyclopropyl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(2,2-difluorocyclopropyl)-7-(3-fluorobenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((1R,2S)-2-methylcyclopropyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((1R,2R)-2-methylcyclopropyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((1 S,2S)-2-methylcyclopropyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((1 S,2R)-2-methylcyclopropyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((2S,3R)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((2S,3S)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((2R,3R)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-6-methyl-3-((2R,3S)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((1R,2S)-2-fluorocyclopropyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((1R,2R)-2-fluorocyclopropyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((1 S,2S)-2-fluorocyclopropyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((1 S,2R)-2-fluorocyclopropyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-cyclopropoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-(difluoromethoxy)benzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-3-(tetrahydro-2H-pyran-4-yl)-7-(4-(trifluoromethoxy)benzyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-(cyclopropylmethoxy)benzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-benzyl-6-ethyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-ethyl-7-(4-methoxybenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-((6-methyl-8-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-7(8H)-yl)methyl)benzonitrile;

4-((6-methyl-8-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-7(8H)-yl)methyl)benzonitrile;

N-(4-((6-methyl-8-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-7(8H)-yl)methyl)phenyl)acetamide;

7-(4-chloro-3-methoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(2-ethylbenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(benzo[d][1,3]dioxol-5-ylmethyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-chloro-4-methoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-aminobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-hydroxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-ethyl-7-(3-fluorobenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((2S,3R)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((2S,3S)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((2R,3R)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((2R,3S)-2-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-propylimidazo[1,5-a]pyrazin-8(7H)-one;

7-((6-methoxypyridin-3-yl)methyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6,7-dimethyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-ethyl-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-7-propyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-isopropyl-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-isopentyl-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(cyclopentylmethyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

2-((6-methyl-8-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-7(8H)-yl)methyl)benzonitrile;

7-(cycloheptylmethyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(3-methyltetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((1R,2R,4S)-2-methyl-7-oxabicyclo[2.2.1]heptan-2-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(4-methoxybenzyl)-6-methyl-3-(1-phenylethyl)imidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(4-methoxybenzyl)-6-methyl-3-(1-phenylethyl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(1,4-dimethylpiperidin-4-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

3-(6-chloro-2,3-dihydro-1H-inden-1-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(3-methyl-5-oxopyrrolidin-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(1-methoxy-2-methylpropan-2-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

3-isopropyl-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-7-((2-methylthiazol-4-yl)methyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-3-(tetrahydro-2H-pyran-4-yl)-7-(thiophen-3-ylmethyl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-3-(tetrahydro-2H-pyran-4-yl)-7-(thiazol-4-ylmethyl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-((3,5-dimethylisoxazol-4-yl)methyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-7-((5-methylisoxazol-3-yl)methyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

6-methyl-7-((3-methylisoxazol-5-yl)methyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(2,6-dimethyltetrahydro-2H-pyran-4-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(cyclohexylmethyl)-6-methyl-3-propylimidazo[1,5-a]pyrazin-8(7H)-one;

3-(2-hydroxypropan-2-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

3-(2-fluoropropan-2-yl)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(7-oxoazepan-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(5-methyltetrahydrofuran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(1-(4-methylthiazol-2-yl)ethyl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(7-(4-methoxybenzyl)-6-methyl-8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-3-yl)-3-methylpyrrolidine-1-sulfonamide;

6-(cyclopentylmethyl)-7-(4-methoxybenzyl)-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(morpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-((tetrahydrofuran-3-yl)amino)imidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(4-methoxybenzyl)-6-methyl-3-(3-methylmorpholino)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(4-methoxybenzyl)-6-methyl-3-(3-methylmorpholino)imidazo[1,5-a]pyrazin-8(7H)-one;

7-(4-methoxybenzyl)-6-methyl-3-(1,4-oxazepan-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

3-(2,2-dimethylmorpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((3aS,6aS)-hexahydro-4H-furo[3,2-b]pyrrol-4-yl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

7-(3-fluorobenzyl)-3-((3aR,6aR)-hexahydro-4H-furo[3,2-b]pyrrol-4-yl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one;

(R)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

(S)-7-(3-fluorobenzyl)-6-methyl-3-(tetrahydro-2H-pyran-3-yl)imidazo[1,5-a]pyrazin-8(7H)-one;

and pharmaceutically acceptable salts of any of these compounds.

13. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt is:

(20) 7-(3-Methoxybenzyl)-6-methyl-3-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-a]pyrazin-8(7H)-one;