IP Library › Granted Patent US 9,969,742

Granted Patent B2

US 9,969,742 · App. 15/386,550 · Granted May 15, 2018

Imidazotriazinone compounds

Inventors: Matthew Gregory Bursavich (Needham, MA); Andrew J. McRiner (Winchester, MA); Amy Ripka (Reading, MA); Gideon Shapiro (Gainesville, FL)

Assignee: Ironwood Pharmaceuticals, Inc.

C07D487/04 C07D519/00

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Patent No.: US 9,969,742
App. No.: 15/386,550
Granted: May 15, 2018
Kind: B2

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Abstract

The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.

Claims (250)

1. A compound selected from the group consisting of:

(+)-2-((3,4-trans)-4-methyl-1-((2-methylpyridin-4-yl)methyl)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-((2-methylpyridin-3-yl)methyl)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-(2,3-dichlorobenzyl)-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-chloro-3-methylbenzyl)-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-chloro-4-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-chloro-3-(trifluoromethyl)benzyl)-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-(2-chloro-5-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-((2-methoxypyrimidin-5-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)-1-(3-chloro-5-(trifluoromethyl)benzyl)-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-(2-chloro-6-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-(2-chloro-3,6-difluorobenzyl)-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-((5-methoxypyridin-3-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-(2-(trifluoromethoxy)benzyl)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-(4-(trifluoromethyl)pyrimidin-2-yl)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-((6-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-fluoro-5-(((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-((4-methylpyridin-2-yl)methyl)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-(thiophen-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-((5-chloropyridin-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)-1-(5-chloro-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)-1-(furan-3-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-(thiophen-3-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-((2-methoxypyridin-4-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-((6-(trifluoromethyl)pyridin-2-yl)methyl)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-((3-(trifluoromethyl)pyridin-2-yl)methyl)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-((5-fluoropyridin-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)-1-((8-fluoroquinolin-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-((1-methyl-1H-pyrazol-5-yl)methyl)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-((5-(trifluoromethyl)pyridin-2-yl)methyl)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-((1-methyl-1H-pyrazol-4-yl)methyl)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-((3-methylpyridin-2-yl)methyl)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-(4-(pyridin-4-yl)benzyl)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-((1-methyl-1H-pyrazol-3-yl)methyl)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-((4-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)-1-(benzo[c][1,2,5]thiadiazol-5-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-(quinolin-8-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-((1-methyl-1H-imidazol-5-yl)methyl)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-((5-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-((tetrahydro-2H-pyran-4-yl)methyl)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-((1-methyl-1H-imidazol-2-yl)methyl)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-(thiazol-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-([1,1′-biphenyl]-4-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-(cyclopropylmethyl)-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-(cyclopentylmethyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(−)-tert-butyl(−)-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)piperidine-1-carboxylate;

(+)-2-((3,4-trans)-4-methyl-1-(oxazol-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-((4,4-difluorocyclohexyl)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-(piperidin-4-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-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)methyl)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-((1-methylpiperidin-4-yl)methyl)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-(pyrazolo[1,5-a]pyridin-3-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-((1,2,4-oxadiazol-5-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-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)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-((2-methylthiazol-4-yl)methyl)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-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)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-((1,2,4-oxadiazol-3-yl)methyl)-4-methylpyrrolidin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

(+)-2-((3,4-trans)-1-((1H-benzo[d]imidazol-2-yl)methyl)-4-methylpyrrolidin-3-yl)-7-(5-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-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(4-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-2-((3,4-trans)-1-((1H-benzo[d]imidazol-2-yl)methyl)-4-methylpyrrolidin-3-yl)-7-(4-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(4-fluorophenyl)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-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-(3-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(3-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(3-fluorophenyl)-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-(3-fluorophenyl)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-7-(3-fluorophenyl)-2-((3,4-trans)-4-methyl-1-(pyridin-3-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-(o-tolyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(o-tolyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(o-tolyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-((1H-benzo[d]imidazol-2-yl)methyl)-4-methylpyrrolidin-3-yl)-7-(o-tolyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(4,5-difluoro-2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-(4,5-difluoro-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-(4,5-difluoro-2-methylphenyl)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-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-phenylimidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-phenylimidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-phenylimidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(4-methylpyridin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(4-methylpyridin-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-7-cyclopentyl-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-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-cyclopentylimidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-7-cyclopentyl-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-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-(pentan-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(pentan-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(pentan-3-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

(+)-2-((3,4-trans)-1-(imidazo[1,2-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(3-methylpyridin-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(3-methylpyridin-4-yl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(2-fluorophenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(2,2,2-trifluoroethyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

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

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

(+)-2-((3,4-trans)-1-([1,2,4]triazolo[1,5-a]pyridin-2-ylmethyl)-4-methylpyrrolidin-3-yl)-7-(2-(trifluoromethyl)phenyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein the compound is selected from the group consisting of: