IMIDAZOTRIAZINONE COMPOUNDS

1 . (canceled)

2 . A compound of Formula (I)

or a pharmaceutically acceptable salt thereof,

wherein:

X is selected from a bond, C(O) or S(O) 2 ;

R 1 is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 1 -C 6 ) alkoxy, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 7 ) cycloalkyloxy, heterocycloalkyl, heterocycloalkyl(C 1 -C 4 )alkyl and heterocycloalkyloxy, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 ) alkyl, OH, —C(O)—(C 1 -C 4 ) alkyl, oxo, CN, (C 1 -C 6 ) alkyl, (C 1 -C 4 )alkoxy, (C 3 -C 7 )cycloalkyl, —C(O)NH(C 1 -C 4 )alkyl, —C(O)N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl], (C 1 -C 4 alkyl)-C(O)—, (C 1 -C 4 )alkylsulfonyl-, —S(O) 2 NH(C 1 -C 4 )alkyl, and —S(O) 2 N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl];

R 2 is independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, heterocycloalkyl, heterocycloalkyl(C 1 -C 4 )alkyl, heteroaryl, heteroaryl(C 1 -C 4 )alkyl, restricted phenyl and restricted phenyl(C 1 -C 4 )alkyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, —C(O(C 1 -C 4 )alkyl, oxo, CN, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkoxy, (C 3 -C 7 )cycloalkyl, —C(O)NH(C 1 -C 4 )alkyl, —C(O)N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl], (C 1 -C 4 alkyl)-C(O)—, (C 1 -C 4 )alkylsulfonyl-, —S(O) 2 NH(C 1 -C 4 )alkyl, and —S(O) 2 N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl]; and

R 3 is independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, heterocycloalkyl, heterocycloalkyl(C 1 -C 4 )alkyl, heteroaryl, heteroaryl(C 1 -C 4 )alkyl, restricted phenyl and restricted phenyl(C 1 -C 4 )alkyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, —C(O(C 1 -C 4 )alkyl, oxo, CN, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkoxy, (C 3 -C 7 )cycloalkyl, —C(O)NH(C 1 -C 4 )alkyl, —C(O)N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl], (C 1 -C 4 alkyl)-C(O)—, (C 1 -C 4 )alkylsulfonyl-, —S(O) 2 NH(C 1 -C 4 )alkyl, and —S(O) 2 N[(C 1 -C 4 )alkyl(C 1 -C 4 )alkyl].

3 . The compound of claim 2 , wherein

X is a bond;

R 1 is independently selected from the group consisting of (C 1 -C 6 )alkyl and (C 1 -C 6 ) alkoxy;

R 2 is independently selected from the group consisting of (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, heterocycloalkyl, heteroaryl, and restricted phenyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkoxy, and (C 1 -C 4 alkyl)-C(O)—; and

R 3 is independently selected from the group consisting of (C 3 -C 7 )cycloalkyl(C 1 -C 4 )alkyl, heterocycloalkyl, heteroaryl(C 1 -C 4 )alkyl, and restricted phenyl(C 1 -C 4 )alkyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, CN, (C 1 -C 6 )alkyl, (C 1 -C 4 )alkoxy, and (C 1 -C 4 alkyl)-C(O)—.

4 . The compound of claim 2 , wherein

X is a bond;

R 1 is (C 1 -C 6 ) alkyl;

R 2 is selected from the group consisting of heterocycloalkyl, (C 3 -C 10 )cycloalkyl, and restricted phenyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(0) 2 (C 1 -C 4 )alkyl, OH, —C(O)—(C 1 -C 4 )alkyl, CN, (C 1 -C 6 )alkyl, and (C 1 -C 4 )alkoxy; and

R 3 is selected from the group consisting of a mono or bicyclic heteroaryl(C 1 -C 4 )alkyl and restricted phenyl(C 1 -C 4 )alkyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, —C(O)—(C 1 -C 4 )alkyl, CN, (C 1 -C 4 )alkyl, and (C 1 -C 4 )alkoxy.

5 . The compound of claim 2 , wherein R 2 is tetrahydropyranyl.

6 . The compound of claim 2 , wherein R 1 is methyl.

7 . The compound of claim 2 , wherein R 3 is pyrimidinylmethyl-, which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, —C(O)—(C 1 -C 4 )alkyl, CN, (C 1 -C 6 )alkyl, and (C 1 -C 4 )alkoxy; or

R 3 is (restricted phenyl)methyl-, which may be optionally substituted with one or more substituents selected from the group consisting of halogen, —S(O) 2 (C 1 -C 4 )alkyl, OH, —C(O)—(C 1 -C 4 )alkyl, CN, (C 1 -C 6 )alkyl, and (C 1 -C 4 )alkoxy.

8 . The compound of claim 2 , wherein the compound is selected from one of the following:

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[1,5-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(imidazo[1,2-b]pyridazin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(imidazo[1,2-b]pyridazin-6-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-(3-fluorobenzyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(4-fluorobenzyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-3-(((3,4-trans)-3-methyl-4-(4-oxo-7-(tetrahydro-2H-pyran-4-yl)-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)pyrrolidin-1-yl)methyl)benzonitrile;

(−)-4-(((3,4-trans)-3-methyl-4-(4-oxo-7-(tetrahydro-2H-pyran-4-yl)-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)pyrrolidin-1-yl)methyl)benzonitrile;

(+)-2-((3,4-trans)-1-(2-fluorobenzyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-(((3,4-trans)-3-methyl-4-(4-oxo-7-(tetrahydro-2H-pyran-4-yl)-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)pyrrolidin-1-yl)methyl)benzonitrile;

(+)-2-((3,4-trans)-4-methyl-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-4-methyl-1-(quinolin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-4-methyl-1-(quinazolin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-(quinolin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-((1s,3R)-adamantan-1-yl)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-((1s,3R)-adamantan-1-yl)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(5-chloro-2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(5-chloro-2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(4-fluoro-2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(4-fluoro-2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(4,4-difluorocyclohexyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(4,4-difluorocyclohexyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-(quinazolin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-(imidazo[1,2-b]pyridazin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-(imidazo[1,2-b]pyridazin-6-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-(pyrazin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-4-methyl-1-(pyrazin-2-ylmethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-((1s,3R)-adamantan-1-yl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one fraction 1;

2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one fraction 2;

2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one fraction 3;

(+)-2-((3,4-trans)-1-((6-methoxypyridin-2-yl)methyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-7-(o-tolyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-(4-fluoro-2-methylphenyl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(4,4-difluorocyclohexyl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-4-methyl-1-((R)-1-phenylethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-4-methyl-1-((S)-1-phenylethyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-(5-chloro-2-methylphenyl)-2-((3,4-trans)-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(furan-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(furan-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-(1-acetylpiperidin-4-yl)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(1-acetylpiperidin-4-yl)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(2-hydroxypropan-2-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(2-hydroxypropan-2-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(1-(ethylsulfonyl)piperidin-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-2-((3,4-trans)-1-benzyl-4-methylpyrrolidin-3-yl)-7-(1-(ethylsulfonyl)piperidin-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-(1-acetylpiperidin-4-yl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(1-acetylpiperidin-4-yl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(1-(ethylsulfonyl)piperidin-4-yl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-7-(1-(ethylsulfonyl)piperidin-4-yl)-2-((3,4-trans)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

or a pharmaceutically acceptable salt thereof.

9 . A pharmaceutical composition comprising the compound of claim 2 , and a pharmaceutically acceptable carrier or excipient.

10 . A method for treating a PDE9 associated disease or disorder comprising administering to a subject an effective amount of a compound of claim 2 , such that the PDE9 associated disease or disorder is treated.

11 . The method of claim 10 , wherein the PDE9 associated disease or disorder is a CNS or neurodegeneration disorder.

12 . The method of claim 11 , wherein the disorder is Alzheimer's disease.

13 . A method of inhibiting PDE9 in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of claim 2 , such that PDE9 is inhibited in the subject.