Btk inhibitors
View Patent ↗The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.
1. A compound according to Formula I, or a pharmaceutically acceptable salt, thereof
wherein:
L is selected from the group consisting of:
R 1 is H, cyano, halogen, (1-4C)alkyl, (3-6C)cycloalkyl, (1-3C)alkoxy, (3-6C)cycloalkoxy, morpholino, aryl or imidazolyl,
wherein (1-4C)alkyl or (1-3C)alkoxy may optionally be substituted with one, two or three halogens;
R 2 is selected from H, (1-3C)alkyl, (1-3C)alkoxy, cyclopropyl, aminocarbonyl,
wherein the (1-3C)alkyl or (1-3C)alkoxy may optionally be substituted with hydroxyl or one, two or three halogen;
R 2a is hydrogen or methyl;
R 3a , R 3b , R 3c and R 3d are each independently selected from H, halogen, (1-3C)alkyl, (1-6C)alkoxy, and (3-6C)cycloalkyl, wherein (1-3C)alkyl may be substituted with hydroxyl or one, two or three halogen;
R 4 is independently selected from the group consisting of:
a) H,
b) halogen, and
c) haloalkyl;
wherein in ring system J-K:
Q is C═O or CH 2 ;
T is C(R e ) 2 , O, NR e , or a bond;
U is C(R d ) 2 , O, or NR d ;
V is CH 2 or O;
R c is independently selected from H, fluoro, methyl or trifluoromethyl,
or two R c groups can join to form a spirofused cyclopropyl group with the carbon atom to which they are attached;
R d is independently selected from H, (1-3C)alkyl or trifluoromethyl;
R e is independently selected from H or (1-6C)alkyl,
or two R e groups can join to form a spirofused cyclopropyl group with the carbon atom to which they are attached;
when T is a bond, Q is C═O and U is C(R d )2,
R c and R d can join to form a 3-6 membered ring with the carbons to which they are attached; and
with the proviso that:
when Q is CH 2 , then T is C(R e ) 2 .
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the ring system J-K is selected from the group consisting of
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein L is
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is trifluoromethyl.
5. The compound of claim 1 having Formula Ia
or a pharmaceutically acceptable salt thereof.
6. A compound selected from the group consisting of:
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(1 S,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-methyltetrahydro-1H-[1,3]oxazolo[4,3-c][1,4]oxazin-3-one;
(1R,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-methyltetrahydro-1H-[1,3]oxazolo[4,3-c][1,4]oxazin-3-one;
(6R,8aS)-6-[8-amino-1-(2-methoxy-4-{2,2,2-trifluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-methoxy-4-{2,2,2-trifluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-hydroxy-1,2-dimethylpropyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[4-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[1-(3-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-hydroxy-1-pyridin-2-ylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-hydroxy-1-pyridin-3-ylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[1-(4-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[2-(hydroxymethyl)-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[2-(hydroxymethyl)-4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-6-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-hydroxy-1-phenylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[2-fluoro-4-(1-hydroxy-1-phenylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-2,2,2-trifluoro-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{2,2,2-trifluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{2,2,2-trifluoro-1-hydroxy-1-[4-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[2,2,2-trifluoro-1-(3-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-{8-amino-1-[2-fluoro-4-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[2-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[2,2,2-trifluoro-1-(4-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-(8-amino-1-{2-methoxy-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{2-methoxy-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-phenylethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[4-(trifluoromethyl)pyridin-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[4-(trifluoromethyl)pyridin-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-tert-butylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-tert-butylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-chlorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-3-methylphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-3-methylphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-(3-methoxyphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-(3-methoxyphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-(3-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-(2-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-(2-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-(2-methoxyphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-(2-methoxyphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-chlorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-(3-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(3-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]propyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethoxy)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethoxy)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-biphenyl-3-yl-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-biphenyl-3-yl-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(3-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]propyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(1R)-1-(4-{8-amino-3-[(6R,8aS)-octahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-1-[3-(trifluoromethyl)phenyl]ethanol;
(1S)-1-(4-{8-amino-3-[(6R,8aS)-octahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-1-[3-(trifluoromethyl)phenyl]ethanol;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-3-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-3-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-hydroxy-1-(3-morpholin-4-ylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-hydroxy-1-(3-morpholin-4-ylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(2-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(2-fluorophenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{hydroxy[3-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{hydroxy[3-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{((1S)-1-hydroxy-1-[3-(1-methylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(1-methylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-2-methyl-1-[3-(trifluoromethyl)phenyl]propyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(2,2,2-trifluoroethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(2,2,2-trifluoroethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-2-methyl-1-[3-(trifluoromethyl)phenyl]propyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[2-(difluoromethyl)-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[2-(difluoromethyl)-4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-cyclobutylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-cyclobutylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
3-[(1S)-1-(4-{8-amino-3-[(6R,8aS)-3-oxooctahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-1-hydroxyethyl]benzonitrile;
3-[(1R)-1-(4-{8-amino-3-[(6R,8aS)-3-oxooctahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-1-hydroxyethyl]benzonitrile;
(6R,8aS)-6-[8-amino-1-(4-{cyclopropyl(hydroxy)[3-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{cyclopropyl(hydroxy)[3-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-cyclopropyl-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-methoxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{((1S)-1-methoxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-ethylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-ethylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-[3-(cyclopropyloxy)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(cyclopropyloxy)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
2-(4-{8-amino-3-[(6R,8aS)-3-oxooctahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
2-(4-{8-amino-3-[(6R,8aS)-3-oxooctahydroindolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl}phenyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(6R,8aS)-6-(8-amino-1-{4-[(1R)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]-3-methoxyphenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{4-[(1S)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]-3-methoxyphenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-chloro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methylphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methylphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-(trifluoromethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1,2-dihydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1,2-dihydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{2,2-difluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{((1S)-1-hydroxy-1-[3-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[5-(trifluoromethyl)thiophen-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{2,2-difluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[5-(trifluoromethyl)thiophen-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(4aS,7R)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2-methyloctahydro-1H-pyrido[1,2-c]pyrimidin-1-one;
(4aS,7R)-7-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2-methyloctahydro-1H-pyrido[1,2-c]pyrimidin-1-one;
(6R,8aS)-6-(8-amino-5-chloro-1-{4-[(1S)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-(8-amino-5-chloro-1-{4-[(1R)-1-(3-cyclopropylphenyl)-1-hydroxyethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3(2H)-one;
(4aR,7S)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2-methyloctahydro-1H-pyrido[1,2-c]pyrimidin-1-one;
(7R,9aS)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2-(1-methylethyl)octahydro-4H-pyrido[1,2-a]pyrazin-4-one;
(7S,9aR)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2-(1-methylethyl)octahydro-4H-pyrido[1,2-a]pyrazin-4-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1R)-1-hydroxy-1-[3-(2,2,2-trifluoroethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1S)-1-hydroxy-1-[3-(2,2,2-trifluoroethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1S)-1-hydroxy-1-[3-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1R)-1-hydroxy-1-[3-(2,2,2-trifluoro-1,1-dimethylethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{[2-fluoro-5-(trifluoromethyl)phenyl](hydroxy)methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{[2-fluoro-5-(trifluoromethyl)phenyl](hydroxy)methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{hydroxy[2-methyl-5-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{[2-fluoro-5-(trifluoromethyl)phenyl](hydroxy)methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{[2-fluoro-5-(trifluoromethyl)phenyl](hydroxy)methyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{hydroxy[2-methyl-5-(trifluoromethyl)phenyl]methyl}phenyl)imidazo[[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-[3-(1,1-difluoroethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(1,1-difluoroethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1S)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[5-(trifluoromethyl)pyridin-3-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[5-(trifluoromethyl)pyridin-3-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[6-(trifluoromethyl)pyridin-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[6-(trifluoromethyl)pyridin-2-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1S)-1-[3-(1,1-difluoroethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(4-{(1R)-1-[3-(1,1-difluoroethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-bicyclo[2.2.2]oct-2-yl-1-hydroxyethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethoxy)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[2-fluoro-5-(trifluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-bicyclo[2.2.2]oct-2-yl-1-hydroxyethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethoxy)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-bicyclo[2.2.2]oct-2-yl-1-hydroxyethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-{8-amino-1-[4-(1-bicyclo[2.2.2]oct-2-yl-1-hydroxyethyl)phenyl]imidazo[1,5-a]pyrazin-3-yl}hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[2-fluoro-5-(trifluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(1H-imidazol-1-yl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(1H-imidazol-1-yl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[2-(trifluoromethyl)pyridin-4-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[2-(trifluoromethyl)pyridin-4-yl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(7S,9aR)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydropyrido[2,1-c][1,4]oxazin-4(3H)-one;
(7R,9aS)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydropyrido[2,1-c][1,4]oxazin-4(3H)-one;
(6R,8aS)-6-[8-amino-5-fluoro-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(2,2-difluorocyclopropyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(2,2-difluorocyclopropyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6S,8aR)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6S,8aR)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(2,2-difluorocyclopropyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(2,2-difluorocyclopropyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-(8-amino-1-{2-ethoxy-4-[1-hydroxy-1-(3-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-(8-amino-1-{2-ethoxy-4-[1-hydroxy-1-(3-methylphenyl)ethyl]phenyl}imidazo[1,5-a]pyrazin-3-yl)hexahydroindolizin-3 (2H)-one;
(3R,8aR)-3-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydro-6H-pyrrolo[2,1-c][1,4]oxazin-6-one;
(7R,9aR)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-difluorooctahydro-4H-quinolizin-4-one;
(7S,9aS)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-difluorooctahydro-4H-quinolizin-4-one;
(1 S,6R,8aR)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-(trifluoromethyl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3(2H)-one;
(7S,9aR)-7-[8-amino-5-chloro-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydropyrido[2,1-c][1,4]oxazin-4(3H)-one;
(7R,9aS)-7-[8-amino-5-chloro-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydropyrido[2,1-c][1,4]oxazin-4(3H)-one;
(7R,9aR)-7-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]tetrahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-4(3H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)-5-fluoroimidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(1R,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-(trifluoromethyl)hexahydroindolizin-3 (2H)-one;
(1R,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-(trifluoromethyl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3(2H)-one;
(1R,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[[1,5-a]pyrazin-3-yl]-1-(trifluoromethyl)hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-fluoro-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(1R,6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1-(trifluoromethyl)hexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-5-fluoro-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethyltetrahydro-1H-[1,3]oxazolo[4,3-c][1,4]oxazin-3-one;
(6′R,8a'S)-6′-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]tetrahydro-5′H-spiro[cyclopropane-1,1′-indolizin]-3′(2′H)-one;
(6′R,8a′S)-6′-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)imidazo[[1,5-a]pyrazin-3-yl]tetrahydro-5′H-spiro[cyclopropane-1,1′-indolizin]-3′(2′H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1l-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-chloro-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1l-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-fluoro-4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-5-fluoro-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1R)-1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}phenyl)-5-fluoroimidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1l-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1l-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)-5-fluoroimidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]-2,2-dimethylhexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-l-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)-5-fluoroimidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethyl)phenyl]-1-hydroxyethyl}-2-fluorophenyl)-5-fluoroimidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]-1,1-dimethylhexahydroindolizin-3(2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethyl)phenyl]-2,2,2-trifluoro-1-hydroxyethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(4-{1-[3-(difluoromethyl)phenyl]-2,2,2-trifluoro-1-hydroxyethyl}-2-methoxyphenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-6-fluoro-4-{(1S)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-6-fluoro-4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(6R,8aS)-6-[8-amino-1-(2-ethoxy-4-{2,2,2-trifluoro-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydroindolizin-3 (2H)-one;
(7′R,9a'S)-7′-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]hexahydro-2′H-spiro[cyclopropane-1,3′-pyrido[1,2-a]pyrazin]-4′-one;
5-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]octahydro-2H-cyclopropa[a]indolizin-2-one(D1);
5-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]octahydro-2H-cyclopropa[a]indolizin-2-one(D2);
5-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]octahydro-2H-cyclopropa[a]indolizin-2-one(D3); and
5-[8-amino-1-(4-{(1R)-1-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl}phenyl)imidazo[1,5-a]pyrazin-3-yl]octahydro-2H-cyclopropa[a]indolizin-2-one(D4);
or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition which comprises the compound of claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.