IP Library › Granted Patent US 9,499,562

Granted Patent B2

US 9,499,562 · App. 14/408,927 · Granted Nov 22, 2016

Substituted thiophene- and furan-fused azolopyrimidine-5-(6H)-one compounds

Inventors: Bryan Branstetter (Carlsbad, CA); James Breitenbucher (Escondido, CA); Brian Dyck (San Diego, CA); Laurent Gomez (San Diego, CA); Andrew Richard Hudson (San Diego, CA); Tami Jo Marrone (Carlsbad, CA); Marco Peters (San Diego, CA); Troy Vickers (San Diego, CA)

Assignee: DART NEUROSCIENCE (CAYMAN) LTD.

C07D495/14 C07D471/14 C07D487/14 C07D491/107 C07D491/147 C07D491/22 C07D495/12 C07D495/22 C07D498/08 C07D519/00

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Quick Facts

Patent No.: US 9,499,562
App. No.: 14/408,927
Granted: Nov 22, 2016
Kind: B2

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Abstract

Described herein are compounds and chemical entities of Formula (I), methods of their synthesis, compositions comprising them, and their use in treating numerous diseases and disorders, including cognitive deficits associated with CNS diseases and disorders.

Claims (520)

1. A chemical entity of Formula I:

wherein:

X is —CH— or —N—;

Y is —O— or —S—;

M is 0-5;

R 1 is each independently selected from the group consisting of: H, halo, —CN, —C 1-6 alkyl, —C 1-6 haloalkyl, —C 1-6 thioalkyl, —C 1-6 alkoxy, —C 1-6 haloalkoxy, —SO 2 C 1-6 alkyl, aryl, heteroaryl, and heterocycloalkyl;

R 3 and R 4 are each independently selected from the group consisting of —H, halo, —C 1-6 alkyl, —C 1-6 haloalkyl, —CH 2 OH, —C 1-6 alkoxy, —C 1-6 haloalkoxy, aryl, optionally substituted 5 or 6 membered heteroaryl, —(C 1 -C 6 alkyl)aryl, —(C 1 -C 6 alkyl)heteroaryl, and —(CR 10 R 11 ) 1-3 NR 12 R 13 ;

or R 3 and R 4 taken together with the carbons to which they are attached form a saturated or unsaturated monocylic ring system, having the following structure:

or R 3 is ((2R,6S)-2,6-dimethylmorpholin-4-yl)methyl, ((2S,6R)-2,6-dimethylmorpholin-4-yl)methyl, (1,4-oxazepan-4-yl)methyl, (1,4-oxazepan-4-ylmethyl), (2,2-dimethylmorpholino)methyl, (3-hydroxyazetidin-1-yl)methyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, (4-acetyl-1,4-diazepan-1-yl)methyl, (4-acetylpiperazin-1-yl)methyl, (4-ethyl-3-oxopiperazin-1-yl)methyl, (4-methylpiperazin-1-yl)methyl, [3-(2-fluorophenoxy)azetidin-1-yl]methyl, [4-(2-fluorophenyl)piperazin-1-yl]methyl, [4-(3-fluorophenyl)piperazin-1-yl]methyl, [4-(4-fluorophenyl)piperazin-1-yl]methyl, [4-(morpholin-4-yl)piperidin-1-yl]methyl, [4-(pyridin-4-yloxy)piperidin-1-yl]methyl, {1,1-difluoro-5-azaspiro [2.4]heptan-5-yl}methyl, 2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl, 4-thiomorpholine-1,1-dione, 7-oxa-2-azaspiro[3.5]nonan-2-ylmethyl, or morpholinomethyl, and R 4 is H or —CH 3 ;

or R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is —N(R 9 )—, and R 9 is H, —C 1-6 alkyl, —C 1-6 haloalkyl, —SO 2 CH 3 , benzyl, benzoyl, (3-chlorobenzyl), (4-chlorobenzyl), (3-chlorobenzoyl), (4-chlorobenzoyl), (2-fluorobenzyl), (4-fluorobenzyl), (pyridin-2-yl), (pyridin-2-ylmethyl), (pyridin-4-ylmethyl), (pyrimidin-2-ylmethyl), (pyrimidin-4-ylmethyl), (pyrazine-2-carbonyl), cyclopropylmethyl, (cyclopropanecarbonyl), (2,2-difluorocyclopropanecarbonyl), (tetrahydro-2H-pyran-4-yl)methyl, (oxetan-3-yl), (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-3-yl)methyl, (tetrahydrofuran-3-carbonyl), (tetrahydro-2H-pyran-2-yl)methyl, (tetrahydro-2H-pyran-4-yl)methyl, (tetrahydro-2H-pyran-3-yl)methyl, (1-methyl-1H-imidazol-2-yl)methyl, (4-methylthiazol-5-yl)methyl, (5-methyl-1,3,4-thiadiazol-2-yl)methyl, (1,1-dioxidothietan-3-yl), (1,4-dioxan-2-yl)methyl), (5-oxotetrahydrofuran-2-yl)methyl, (1-methylpyrrolidine-3-carbonyl), (pyrrolidine-3-carbonyl), or (morpholin-2-ylmethyl);

D is —O—, —N(R 9 )—, or a bond;

m and n are each independently 0-4, with the proviso that the sum of m and n is 1-5 when D is —O—, —N(R 9 )—, or is 2-6 when D is a bond; and with the proviso that when D is a bond, R 1 is not —Cl in the para position;

R 5 , R 6 , R 7 , R 8 , are each independently selected from the group consisting of: —H, —F, —C 1-6 alkyl, —C 1-6 haloalkyl, —OH, —C 1-6 alkoxy, —C 1-6 haloalkoxy;

R 9 is selected from the group consisting of —H, —C 1-6 alkyl, —C 1-6 thioalkyl, —C 1-6 haloalkyl, —CO 2 C 1-6 alkyl, —SO 2 (C 1-6 alkyl), —C 1-6 alkyl(aryl), —C 1-6 alkyl(C 3-6 cycloalkyl), —C 1-6 alkyl(heterocycloalkyl), —C 1-6 alkyl(heteroaryl), heteroaryl, —CO(aryl), —CO(heteroaryl), —CO(heterocycloalkyl), —CO(C 3-6 cycloalkyl), wherein each aryl, cycloalkyl, heterocycloalkyl, heteroaryl are optionally unsubstituted or substituted with a member each independently selected from the group consisting of —H, —Cl, —F, and —CH 3 ;

R 10 and R 11 are each independently selected from the group consisting of —H, —F, —C 1-6 alkyl, —CF 3 and —OH;

R 12 and R 13 are each independently selected from the group consisting of —H, —C 1-6 alkyl, —C 3-6 cycloalkyl, —C 1-6 alkyl(aryl), —C 1-6 alkyl(heteroaryl), —C 1-6 alkyl(heterocycloalkyl), —CH 2 CON(C 1-6 alkyl) 2 ;

or R 12 is H or —C 1-6 alkyl and R 13 is —CH 3 , —CH 2 CON(CH 3 ) 2 , cyclopropyl, benzyl, 3-pyridyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl, (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-2-yl)methyl or (tetrahydrofuran-3-yl)methyl;

or R 12 is H, —C 1-6 alkyl, R 13 is —CH 3 , —CH 2 CON(CH 3 ) 2 , cyclopropyl, benzyl, 3-pyridyl, (tetrahydrofuran-2-yl)methyl, (tetrahydrofuran-3-yl)methyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl or (3-methyloxetan-3-yl)methyl;

or R 12 and R 13 are taken together with the nitrogen to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more R 14 , where each R 14 is independently selected from the group consisting of —H, —C 1-6 alkyl, —CH 2 OH, —OH, —COCH 3 , —SO 2 CH 3 , —O-pyridyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, —O-phenyl, —O-(2-fluorophenyl), -morpholino, 1,1-difluoro-cyclopropyl, or two R 14 members are taken together to form a —C 3-6 heterocycloalkyl;

or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a heterocycloalkyl ring selected from (2R,6S)-2,6-dimethylmorpholine, (2S,6R)-2,6-dimethylmorpholine, (3R,5 S)-3,5-dimethylpiperazine, 1,1-difluoro-5-azaspiro[2.4]heptane, 1,4-oxazepane, 2-(methoxymethyl)pyrrolidine, 2,2-dimethylmorpholine, 2,6-dimethylmorpholine, 2-ethylmorpholine, 2-methylmorpholine, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-(2-fluorophenoxy)azetidine, 3,3,4-trimethylpiperazine, 3,4-dimethylpiperazine, 3-hydroxyazetidine, 3-methylmorpholine, 3-oxopiperazine, 4-(2-fluorophenyl)piperazine, 4-(3-fluorophenyl)piperazine, 4-(4-fluorophenyl)piperazine, 4-(methylsulfonyl)piperazine, 4-(morpholin-4-yl)piperidine, 4-(pyridin-4-yloxy)piperidine, 4-acetyl-1,4-diazepane, 4-acetylpiperazine, 4-ethyl-3-oxopiperazine, 4-hydroxypiperidine, 4-isopropylpiperazine, 4-methyl-piperazine, 4-thiomorpholine-1,1-dione, 8-oxa-3-azabicyclo[3.2.1]octane, isoindoline, morpholine, octahydropyrrolo[1,2-a]pyrazine, piperazine, and pyrrolidine;

wherein the chemical entity is selected from the group consisting of compounds of Formula (I), and pharmaceutically acceptable salts of compounds of Formula (I).

2. The chemical entity of claim 1 , wherein Y is —S—.

3. The chemical entity of claim 1 , wherein M is 1, 2 or 3.

4. The chemical entity of claim 2 , wherein R 1 is —OCH 3 .

5. The chemical entity of claim 2 , wherein R 1 is —F, —Cl, —Br, —CF 3 , —CN or —CHF 2 .

6. The chemical entity of claim 1 , wherein R 3 is H, —Br, —C 1-6 alkyl, benzyl, 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl and R 4 is H or —CH 3 .

7. The chemical entity of claim 1 , wherein R 3 is —(CR 10 R 11 ) 1-3 NR 12 R 13 and R 4 is H or —CH 3 .

8. The chemical entity of claim 1 , wherein R 3 is H, —Br, —C 1-5 alkyl, benzyl, 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl, or —(CR 10 R 11 )NR 12 R 13 , where R 10 and R 1 are each H, R 12 is H or —C 1-6 alkyl, R 13 is —CH 3 , —CH 2 CON(CH 3 ) 2 , cyclopropyl, benzyl, 3-pyridyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl, (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-2-yl)methyl or (tetrahydrofuran-3-yl)methyl and R 4 is H or —CH 3 .

9. The chemical entity of claim 1 , wherein R 3 is —(CR 10 R 11 )NR 12 R 13 , where R 10 and R 11 are each H, R 12 is H, —C 1-6 alkyl, R 13 is —CH 3 , —CH 2 CON(CH 3 ) 2 , cyclopropyl, benzyl, 3-pyridyl, (tetrahydrofuran-2-yl)methyl, (tetrahydrofuran-3-yl)methyl, oxan-4-ylmethyl, 2,2-dimethyloxan-4-yl or (3-methyloxetan-3-yl)methyl and R 4 is H or —CH 3 .

10. The chemical entity of claim 1 , wherein R 3 is H or —CH 3 and R 4 is —(CR 10 R 11 ) 1-3 NR 12 R 13 .

11. The chemical entity of claim 1 , wherein R 3 is H or —CH 3 , R 4 is —(CR 10 R 11 )NR 12 R 13 , where R 10 and R 11 are each H, R 12 is H or —C 1-6 alkyl, and R 13 is —C 1-6 alkyl or oxan-4-ylmethyl.

12. The chemical entity of claim 1 , wherein R 3 or R 4 is —(CR 10 R 11 ) 1-3 NR 12 R 13 , R 10 and R 11 are each independently H, —CH 3 , or —OH, and R 12 and R 13 are taken together with the nitrogen to which they are attached to form a heterocycloalkyl ring selected from (2R,6 S)-2,6-dimethylmorpholine, (2S,6R)-2,6-dimethylmorpholine, (3R,5S)-3,5-dimethylpiperazine, 1,1-difluoro-5-azaspiro[2.4]heptane, 1,4-oxazepane, 2-(methoxymethyl)pyrrolidine, 2,2-dimethylmorpholine, 2,6-dimethylmorpholine, 2-ethylmorpholine, 2-methylmorpholine, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-(2-fluorophenoxy)azetidine, 3,3,4-trimethylpiperazine, 3,4-dimethylpiperazine, 3-hydroxyazetidine, 3-methylmorpholine, 3-oxopiperazine, 4-(2-fluorophenyl)piperazine, 4-(3-fluorophenyl)piperazine, 4-(4-fluorophenyl)piperazine, 4-(methylsulfonyl)piperazine, 4-(morpholin-4-yl)piperidine, 4-(pyridin-4-yloxy)piperidine, 4-acetyl-1,4-diazepane, 4-acetylpiperazine, 4-ethyl-3-oxopiperazine, 4-hydroxypiperidine, 4-isopropylpiperazine, 4-methyl-piperazine, 4-thiomorpholine-1,1-dione, 8-oxa-3-azabicyclo[3.2.1]octane, isoindoline, morpholine, octahydropyrrolo[1,2-a]pyrazine, piperazine, and pyrrolidine.

13. The chemical entity of claim 1 , wherein R 3 is ((2R,6S)-2,6-dimethylmorpholin-4-yl)methyl, ((2S,6R)-2,6-dimethylmorpholin-4-yl)methyl, (1,4-oxazepan-4-yl)methyl, (1,4-oxazepan-4-ylmethyl), (2,2-dimethylmorpholino)methyl, (3-hydroxyazetidin-1-yl)methyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, (4-acetyl-1,4-diazepan-1-yl)methyl, (4-acetylpiperazin-1-yl)methyl, (4-ethyl-3-oxopiperazin-1-yl)methyl, (4-methylpiperazin-1-yl)methyl, [3-(2-fluorophenoxy)azetidin-1-yl]methyl, [4-(2-fluorophenyl)piperazin-1-yl]methyl, [4-(3-fluorophenyl)piperazin-1-yl]methyl, [4-(4-fluorophenyl)piperazin-1-yl]methyl, [4-(morpholin-4-yl)piperidin-1-yl]methyl, [4-(pyridin-4-yloxy)piperidin-1-yl]methyl, {1,1-difluoro-5-azaspiro[2.4]heptan-5-yl}methyl, 2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl, 4-thiomorpholine-1,1-dione, 7-oxa-2-azaspiro[3.5]nonan-2-ylmethyl, or morpholinomethyl, and R 4 is H or —CH 3 .

14. The chemical entity of claim 1 , wherein R 3 is morpholinomethyl, (2,2-dimethylmorpholino)methyl, 2,6-dimethylmorpholino)methyl, ((2S,6R)-2,6-dimethylmorpholino)methyl, ((2R,6S)-2,6-dimethylmorpholin-4-yl)methyl, (4-(methylsulfonyl)piperazin-1-yl)methyl, 1-hydroxy-2-morpholinoethyl or 2-((2S,6R)-2,6-dimethylmorpholino)-1-hydroxyethyl, and R 4 is H or —CH 3 .

15. The chemical entity of claim 1 , wherein R 4 is ((2S,6R)-2,6-dimethylmorpholino)methyl, ((2R,6S)-2,6-dimethylmorpholin-4-yl)methyl, [(3-phenoxypyrrolidin-1-yl)methyl], [3-(hydroxymethyl)-3-(2-methylpropyl)piperidin-1-yl]methyl, [ethyl(oxan-4-ylmethyl)amino]methyl, [methyl(oxan-4-ylmethyl)amino]methyl, [(oxan-4-ylmethyl)amino]methyl, or [bis(propan-2-yl)amino]methyl.

16. The chemical entity of claim 1 , wherein R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is —O—, and m is 1 and n is 2.

17. The chemical entity of claim 1 , wherein R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is —N(R 9 )—, and m is 0, 1, or 2 and n is 1, 2 or 3; with the proviso that the sum of m and n is 1-5.

18. The chemical entity of claim 1 , wherein R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is a bond and m and n are 2.

19. The chemical entity of claim 1 , wherein R 5 , R 6 , R 7 , R 8 , are each independently —H, —F, or —CH 3 .

20. The chemical entity of claim 1 , wherein R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein D is —N(R 9 )—, and R 9 is H, —C 1-6 alkyl, —C 1-6 haloalkyl, —SO 2 CH 3 , benzyl, benzoyl, (3-chlorobenzyl), (4-chlorobenzyl), (3-chlorobenzoyl), (4-chlorobenzoyl), (2-fluorobenzyl), (4-fluorobenzyl), (pyridin-2-yl), (pyridin-2-ylmethyl), (pyridin-4-ylmethyl), (pyrimidin-2-ylmethyl), (pyrimidin-4-ylmethyl), (pyrazine-2-carbonyl), cyclopropylmethyl, (cyclopropanecarbonyl), (2,2-difluorocyclopropanecarbonyl), (oxetan-3-yl), (3-methyloxetan-3-yl)methyl, (tetrahydrofuran-3-yl)methyl, (tetrahydrofuran-3-carbonyl), (tetrahydro-2H-pyran-2-yl)methyl, (tetrahydro-2H-pyran-4-yl)methyl, (tetrahydro-2H-pyran-3-yl)methyl, (1-methyl-1H-imidazol-2-yl)methyl, (4-methylthiazol-5-yl)methyl, (5-methyl-1,3,4-thiadiazol-2-yl)methyl, (1,1-dioxidothietan-3-yl), (1,4-dioxan-2-yl)methyl), (5-oxotetrahydrofuran-2-yl)methyl, (1-methylpyrrolidine-3-carbonyl), (pyrrolidine-3-carbonyl), or (morpholin-2-ylmethyl).

21. The chemical entity of claim 1 , wherein R 3 and R 4 taken together with the carbons to which they are attached form a six member monocyclic ring system, wherein each R 5 , R 6 , R 7 , R 8 , are independently —H and —F; D is —N(R 9 )—, and R 9 is (tetrahydrofuran-3-yl)methyl or (tetrahydro-2H-pyran-4-yl)methyl.

22. A compound selected from the group consisting of:

6-(2-Chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-Benzyl-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Benzyl-6-(2-chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Benzyl-6-(3-chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Chlorobenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chlorobenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-Benzyl-8-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Chlorobenzyl)-8-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)-8-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-8-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chlorobenzyl)-8-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6, 8-Dibenzylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)-8-benzylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Chlorobenzyl)-8-isopentylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chlorobenzyl)-8-isopentylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)-8-isopentylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Benzyl-6-(4-chlorobenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-8-isopentylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-Benzylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-Benzyl-8-isopentylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((1,4-Oxazepan-4-yl)methyl)-6-(4-methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Dimethylamino)methyl)-6-(4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-(morpholinomethyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((4-methylpiperazin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((2S,6R)-2,6-Dimethylmorpholino)methyl)-6-(4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Ethyl-3-oxopiperazin-1-yl)methyl)-6-(4-methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((2,2-dimethylmorpholino)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(2-oxa-5-azabicyclo [2.2.1]heptan-5-ylmethyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(7-oxa-2-azaspiro [3.5]nonan-2-ylmethyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(2-Oxa-7-azaspiro [3.5]nonan-7-ylmethyl)-6-(4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

7-((6-(4-Methoxybenzyl)-5-oxo-5,6-dihydrothieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-8-yl)methyl)tetrahydro-1H-oxazolo[3,4-a]pyrazin-3 (5H)-one;

6-(4-Methoxybenzyl)-8-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(3,5-Dimethylisoxazol-4-yl)-6-(4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-(pyrrolidin-1-ylmethyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-(morpholinomethyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Dimethylamino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Cyclopropyl(methyl)amino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Hydroxypiperidin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Benzyl(2-hydroxyethyl)amino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-(piperazin-1-ylmethyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((((3-methyloxetan-3-yl)methyl)amino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Acetylpiperazin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-(((pyridin-3-ylmethyl)amino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((3-oxopiperazin-1-yl)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((methyl((tetrahydrofuran-2-yl)methyl)amino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((2S,6R)-2,6-Dimethylmorpholino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(Isoindolin-2-ylmethyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Cyclopropylamino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

(S)-6-(4-Methoxybenzyl)-8-((2-(methoxymethyl)pyrrolidin-1-yl)methyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((methyl((tetrahydrofuran-3-yl)methyl)amino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

2-(((6-(4-Methoxybenzyl)-9-methyl-5-oxo-5,6-dihydrothieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-8-yl)methyl)(methyl)amino)-N,N-dimethylacetamide;

8-((1,4-Oxazepan-4-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((4-methylpiperazin-1-yl)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Isopropylpiperazin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(2-Oxa-5-azabicyclo [2.2.1]heptan-5-ylmethyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Ethyl-3-oxopiperazin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(8-Oxa-3-azabicyclo [3.2.1]octan-3-ylmethyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((2-Ethylmorpholino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((2,2-Dimethylmorpholino)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((2-methylmorpholino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((3-methylmorpholino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((3R,5 S)-3,5-Dimethylpiperazin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((3,4-Dimethylpiperazin-1-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-methyl-8-((3,3,4-trimethylpiperazin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

(S)-8-((Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)methyl)-6-(4-methoxybenzyl)-9-methylthieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Bromo-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(Hydroxymethyl)-6-(4-methoxybenzyl)-9-methylthieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(((2S,6R)-2,6-Dimethylmorpholino)methyl)-6-(4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-8,9-dimethylfuro[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

tert-Butyl 6-(4-methoxybenzyl)-5-oxo-5,6,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-9(8H)-carboxylate;

6-(2-Chlorobenzyl)-8,9,10,11-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

4-(4-Methoxybenzyl)-2-(morpholinomethyl)pyrazolo[1,5-c]thieno [3,2-e]pyrimidin-5(4H)-one;

6-(4-Chlorobenzyl)-10,10-dimethyl-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-Benzyl-8,9,10,11-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chlorobenzyl)-8,9,10,11-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-([1,1′-Biphenyl]-4-ylmethyl)-8,9,10,11-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Methylbenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-(Trifluoromethyl)benzyl)-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Methoxybenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(3,4-Dichlorobenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Fluorobenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Chloro-3-fluorobenzyl)-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Chloro-2-fluorobenzyl)-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(3-Fluoro-4-methoxybenzyl)-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-(Trifluoromethoxy)benzyl)-6, 8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Ethoxybenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(3,5-Difluoro-4-methoxybenzyl)-6,8,10,11-tetrahydro-5H-pyrano[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-one;

6-(4-Chlorobenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3,4-Dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-methyl-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-Benzyl-6-(4-chlorobenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-(cyclopropylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

2-(((2 S, 6R)-2,6-Dimethylmorpholino)methyl)-4-(4-methoxybenzyl)pyrazolo[1,5-c]thieno [3,2-e]pyrimidin-5(4H)-one;

6-(4-Chlorobenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-(oxetan-3-yl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-(2,2,2-trifluoroethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(Cyclopropylmethyl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((3-methyloxetan-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(3-(methylthio)propyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((tetrahydrofuran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-((2,2-Difluorobenzo [d][1,3]dioxol-5-yl)methyl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-neopentyl-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyrimidin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(3-(methylsulfonyl)propyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyrimidin-4-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyridin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyridin-4-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((1-methyl-1H-imidazol-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((4-methylthiazol-5-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(1,1-Dioxidothietan-3-yl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-((1,4-Dioxan-2-yl)methyl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((5-oxotetrahydrofuran-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(4-Fluorobenzyl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(2-Fluorobenzyl)-6-(4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-(pyridin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-((1-methyl-1H-imidazol-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-(pyrimidin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-((tetrahydrofuran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

11,11-Difluoro-6-(4-methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

11,11-Difluoro-6-(4-methoxybenzyl)-9-((tetrahydro-2H-pyran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-(pyrimidin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-((1-methyl-1H-imidazol-2-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-(pyridin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-((tetrahydrofuran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-((tetrahydro-2H-pyran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((tetrahydrofuran-3-yl)methyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

6-(4-Methoxybenzyl)-9-((1-methyl-1H-imidazol-2-yl)methyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

6-(4-Methoxybenzyl)-9-(pyrimidin-2-ylmethyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

6-(4-Methoxybenzyl)-9-(pyridin-2-ylmethyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

6-(4-Methoxybenzyl)-8-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((tetrahydro-2H-pyran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((tetrahydrofuran-3-yl)methyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(1,1-Difluoropropan-2-yl)-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(4-Chlorobenzyl)-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(4-Chlorobenzyl)-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Benzyl-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(3-Chlorobenzyl)-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

11,11-Difluoro-6-(2-fluoro-4-methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-(pyrazine-2-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chlorobenzyl)-9-(cyclopropanecarbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(Cyclopropanecarbonyl)-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(2,2-Difluorocyclopropanecarbonyl)-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(methylsulfonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(1-methylpyrrolidine-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-(cyclopropanecarbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Chloro-2-fluorobenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

11,11-Difluoro-6-(4-Methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-(Cyclopropanecarbonyl)-6-(2-fluoro-4-methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

(R)-6-(4-Methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

(R)-6-(4-Methoxybenzyl)-9-(tetrahydrofuran-3-carbonyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

9-(Cyclopropanecarbonyl)-6-(4-Methoxybenzyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

8-(Cyclopropanecarbonyl)-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-(tetrahydrofuran-3-carbonyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-Benzoyl-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(3-Chlorobenzoyl)-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(4-Chlorobenzoyl)-6-(3,4-dimethoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyridin-2-yl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(morpholin-2-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(pyrrolidine-3-carbonyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,4′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-(piperidin-4-ylmethyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((4-(pyridin-4-yloxy)piperidin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-(2-Fluorophenyl)piperazin-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-(3-Fluorophenyl)piperazin-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-(4-Fluorophenyl)piperazin-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((3-phenoxypyrrolidin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((3-(2-Fluorophenoxy)azetidin-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((4-morpholinopiperidin-1-yl)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((1,1-Difluoro-5-azaspiro[2.4]heptan-5-yl)methyl)-6-(4-Methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((4-Acetyl-1,4-diazepan-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((1,4-Oxazepan-4-yl)methyl)-6-(2,3-difluoro-4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-((3-(Hydroxymethyl)-3-isobutylpiperidin-1-yl)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((2,2-Dimethyltetrahydro-2H-pyran-4-yl)(ethyl)amino)methyl)-6-(4-Methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-((Ethyl((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)-6-(4-Methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((Ethyl((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)-6-(4-Methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((methyl((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2,3-Difluoro-4-methoxybenzyl)-8-(((2R,6S)-2,6-dimethylmorpholino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((2R,6S)-2,6-Dimethylmorpholino)methyl)-6-(3-fluoro-4-methoxybenzyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-(((2R,6S)-2,6-Dimethylmorpholino)methyl)-6-(2-fluoro-4-methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-9-((((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((methyl(tetrahydro-2H-pyran-4-yl)amino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chloro-4-fluorobenzyl)-8-(((2R,6S)-2,6-dimethylmorpholino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

8-((1,1-Dioxidothiomorpholino)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Fluoro-4-methoxybenzyl)-8-(morpholinomethyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-8-(morpholinomethyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(3-Chloro-4-fluorobenzyl)-8-(morpholinomethyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2,3-Difluoro-4-methoxybenzyl)-8-((methyl((3-methyloxetan-3-yl)methyl)amino)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8-((((3-methyloxetan-3-yl)methyl)amino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2,3-Difluoro-4-methoxybenzyl)-8-((3-hydroxyazetidin-1-yl)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2-Fluoro-4-methoxybenzyl)-8-((3-hydroxyazetidin-1-yl)methyl)thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(2,3-Difluoro-4-methoxybenzyl)-8-((dimethylamino)methyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

9-((Diisopropylamino)methyl)-6-(4-Methoxybenzyl)thieno [3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-10-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[3′,4′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-6,8,9,10,11,12-hexahydro-5H-[1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:4,5]thieno[2,3-c]azepin-5-one;

11,11-Difluoro-9-isobutyl-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

11,11-Difluoro-6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

6-(4-Methoxybenzyl)-8,9,10,11-tetrahydropyrido[3′,2′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;

and pharmaceutically acceptable salts thereof.

23. A pharmaceutical composition comprising an effective amount of a chemical entity of Formula (I):

wherein:

X is —CH— or —N—;

Y is —O— or —S—;

M is 0-5;

R 1 is each independently selected from the group consisting of H, halo, —CN, —C 1-6 alkyl, —C 1-6 haloalkyl, —C 1-6 thioalkyl, —C 1-6 alkoxy, —C 1-6 haloalkoxy, —SO 2 C 1-6 alkyl, aryl, heteroaryl, and heterocycloalkyl;

or R 3 and R 4 taken together with the carbons to which they are attached form a saturated or unsaturated monocylic ring system, having the following structure:

D is —O—, —N(R 9 )—, or a bond;

R 5 , R 6 , R 7 , R 8 , are each independently selected from the group consisting of —H, —F, —C 1-6 alkyl, —C 1-6 haloalkyl, —OH, —C 1-6 alkoxy, —C 1-6 haloalkoxy;

R 10 and R 11 are each independently selected from the group consisting of —H, —F, —C 1-6 alkyl, —CF 3 , and —OH;

wherein the chemical entity is selected from the group consisting of compounds of Formula (I), and pharmaceutically acceptable salts of compounds of Formula (I).

24. A pharmaceutical composition comprising an effective amount of a compound of claim 22 ; and a pharmaceutically acceptable excipient.

25. A compound of Formula I:

or pharmaceutically acceptable salt thereof,

wherein:

X is —CH— or —N—;

Y is —O— or —S—;

M is 0-5;

or R 3 and R 4 taken together with the carbons to which they are attached form a saturated or unsaturated monocylic ring system, having the following structure:

D is —O—, —N(R 9 )—, or a bond;

R 5 , R 6 , R 7 , R 8 , are each independently selected from the group consisting of —H, —F, —C 1-6 alkyl, —C 1-6 haloalkyl, —OH, —C 1-6 alkoxy, —C 1-6 haloalkoxy;

R 10 and R 11 are each independently selected from the group consisting of —H, —F, —C 1-6 alkyl, —CF 3 and —OH;

or R 12 and R 13 are taken together with the nitrogen to which they are attached form a heterocycloalkyl ring, optionally substituted with one or more R 14 , where each R 14 is independently selected from the group consisting of: —H, —C 1-6 alkyl, —CH 2 OH, —OH, —COCH 3 , —SO 2 CH 3 , —O-pyridyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, —O-phenyl, —O-(2-fluorophenyl), -morpholino, 1,1-difluoro-cyclopropyl, or two R 14 members are taken together to form a —C 3-6 heterocycloalkyl.

26. A compound selected from the group consisting of: