Substituted pyridizinone derivatives as PDE10 inhibitors
View Patent ↗The present invention is directed to substituted pyridizinone compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
1. A compound of the formula I:
wherein:
R is hydrogen, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, or (CH 2 ) n C 5-10 heteroaryl said heteroaryl optionally substituted with 1 to 3 groups of R a ;
R 1 is hydrogen, C 1-6 alkyl or halogen, said alkyl optionally substituted with 1 to 3 groups of R a ;
R 2 is C 1-6 alkyl, or (CH 2 ) n C 6-10 aryl, said aryl optionally substituted with 1 to 3 groups of R a ;
A is C 5-10 heteroaryl optionally substituted with 1 to 3 groups of R a ;
B is (CH 2 ) n C 6-10 aryl, (CH 2 ) n C 5-10 heteroaryl, —C(O)(CH 2 ) n C 6-10 aryl, or —C(O)(CH 2 ) n C 5-10 heteroaryl, said aryl and heteroaryl optionally substituted with 1 to 3 groups of R a ;
R a selected from the group consisting of:
(1) (CH 2 ) n O 0-1 C 1-4 haloalkyl,
(2) halogen,
(3) (CH 2 ) n OR,
(4) C 1-6 alkyl,
(5) (CH 2 ) n C 3-6 cycloalkyl,
(6) (CH 2 ) n C 6-10 aryl, said aryl optionally substituted with one or more of OR, or C 1-6 alkyl;
(7) —(CH 2 ) n CO 2 R,
(8) —(CH 2 ) n CN,
(9) S(O) p R,
(10) C 2-6 alkenyl,
(11) —N(R) 2 ,
n is 0, 1, 2, 3, or 4,
p is 0, 1, or 2,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 wherein A is selected from the group consisting of pyridyl, quinolinyl, pyrazolyl, indazolyl, and cyclopentapyridinyl said of pyridyl, quinolinyl, pyrazolyl, indazolyl, and cyclopentapyridinyl optionally substituted with 1 to 3 groups of R a .
3. The compound according to claim 2 wherein A is optionally substituted pyridyl or pyrazolyl.
4. The compound according to claim 1 wherein B is selected from the group consisting of (CH 2 ) n C 6-10 aryl and (CH 2 ) n C 5-10 heteroaryl and the aryl or heteroaryl is isoxazolyl, pyrimidinyl, pyradizinyl, pyrazolopyridinyl, triazolyl thiazolyl, thiadiazolyl, phenyl, pyridyl, or pyrazolyl, said isoxazolyl, pyrimidinyl, pyradizinyl, pyrazolopyridinyl, triazolyl thiazolyl, thiadiazolyl, phenyl, pyridyl, and pyrazolyl are optionally substituted with 1 to 3 groups of R a .
5. The compound according to claim 1 wherein B is selected from the group consisting of —C(O)C 6-10 aryl and —(CO)C 5-10 heteroaryl and the aryl or heteroaryl is isoxazolyl, pyrimidinyl, pyradizinyl, pyrazolopyridinyl, triazolyl thiazolyl, thiadiazolyl, phenyl, pyridyl, or pyrazolyl, said isoxazolyl, pyrimidinyl, pyradizinyl, pyrazolopyridinyl, triazolyl thiazolyl, thiadiazolyl, phenyl, pyridyl, and pyrazolyl are optionally substituted with 1 to 3 groups of R a .
6. The compound according to claim 3 wherein B is optionally substituted CH 2 thiazolyl, CH 2 pyridyl, or CH 2 pyrazolyl.
7. The compound according to claim 4 wherein B is optionally substituted CH 2 thiazolyl, CH 2 pyridyl, or CH 2 pyrazolyl.
8. The compound according to claim 1 wherein A is optionally substituted pyridyl and B is optionally substituted CH 2 thiazoly, CH 2 pyridyl, or CH 2 pyrazolyl.
9. The compound according to claim 1 wherein A is optionally substituted pyrazolyl and B is optionally substituted CH 2 thiazoly, CH 2 pyridyl, or CH 2 pyrazolyl.
10. The compound according to claim 1 wherein A is optionally substituted quinolinyl, pyridyl, pyrazolyl or indazolyl and B is selected from the group consisting of -optionally substituted C(O)C 6-10 aryl and —(CO)C 5-10 heteroaryl and the aryl or heteroaryl is isoxazolyl, pyrimidinyl, pyradizinyl, pyrazolopyridinyl, triazolyl thiazolyl, thiadiazolyl, phenyl, pyridyl, or pyrazolyl.
11. The compound according to claim 1 which is represented by formula Ia, Iaa or Ib:
wherein R, A, and B are as defined herein; or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 1 represented by structural formula Ic:
wherein R, and B are as defined herein and R b is R a ; or a pharmaceutically acceptable salt thereof.
13. The compound according to claim 1 represented by structural formula Id:
wherein R, and B are as defined herein, or a pharmaceutically acceptable salt thereof.
14. A compound which is:
2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)-6-(((1S,2S)-2-(5-methyl pyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-(2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-4-(5-methyl-1,3,4-thiadiazol-2-yl)methylamino)-6-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-(difluoromethoxy)pyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)-methylamino)-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclo-propyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methyl-amino)pyridazin-3(2H)one,
4-(4-methoxybenzylamino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((5-methylpyridin-2-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((6-methylpyridin-3-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclo-propyl)methoxy)-4-((4-methylthiazol-2-yl)methyl-amino)pyridazin-3(2H)one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
4-((1,3-dimethyl-1H-pyrazol-5-yl)methylamino-)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-fluoro-pyridin-2-yl)-cyclopropyl-)methoxy)-4-(4-methoxybenzylamino)-2-methyl-pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methylpyridin-2-yl)methylamino)pyridazin-3(2H)-one,
4-(4-methoxybenzylamino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(4-(((1S,2S)-2-(5-(difluoromethoxy)pyridin-2-yl)cyclopropyl)-methoxy)-2-methyl-pyrimidin-5-yl)-1-methylpyridin-2(1H)-one,
6-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclo-propyl)methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino-)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((6-methylpyridin-3-yl)methylamino)pyridazin-3(2H)-one,
4-((1,3-dimethyl-1H-pyrazol-5-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((1-methyl-1H-pyrazol-4-yl)methylamino)-pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)-cyclopropyl)methoxy)-4-((5-methylpyridin-2-yl)-methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-chloropyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-chloro-pyridin-2-yl)cyclopropyl)-methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-(difluoro-methoxy)pyridin-2-yl)-cyclopropyl)-methoxy)-4-((1,3-dimethyl-1H-pyrazol-5-yl)methyl-amino)-2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(5-(difluoromethoxy)pyridin-2-yl)cyclopropyl)-methoxy)-2-methyl-4-((2-methylthiazol-5-yl)methyl-amino)pyridazin-3(2H)one,
6-(((1S,2S)-2-(5-(difluoromethoxy)pyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-fluoropyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-chloropyridin-2-yl)cyclopropyl)methoxy)-4-((1,3-dimethyl-1H-pyrazol-5-yl)methylamino)-2-methylpyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-chloropyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
4-((4-chloro-1,3-dimethyl-1H-pyrazol-5-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-4-(methyl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)amino)-6-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-((1,3-dimethyl-1H-pyrazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-((5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-((5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-(((5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)amino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-(((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)amino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)-cyclopropyl)methoxy)-4-(((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-amino)pyridazin-3(2H)one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((thiazol-5-ylmethyl)-amino)pyridazin-3(2H)one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((thiazol-5-ylmethyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((thiazol-5-ylmethyl)amino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((thiazol-2-ylmethyl)amino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-(((2-methylthiazol-4-yl)methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((2-methylthiazol-4-yl)methyl)amino-)pyridazin-3(2H)-one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-6-(((1S,2S)-2-(5-fluoro-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-chloro-pyridin-2-yl)cyclopropyl-)methoxy)-4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methylpyridazin-3(2H)one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(pyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methylpyridazin-3(2H)-one,
4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(quinolin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-(difluoromethoxy)pyridin-2-yl)cyclopropyl)methoxy)-4-(((2,6-dimethylpyridin-3-yl)methyl)amino)-2-methylpyridazin-3(2H)-one,
4-(((3,5-dimethylisoxazol-4-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-pyridazin-3(2H)-one,
4-(((3,5-dimethylisoxazol-4-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclo-propyl)methoxy)pyridazin-3(2H)-one,
4-(((3,5-dimethylisoxazol-4-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-(((2-methylpyridin-4-yl)methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((pyrimidin-5-ylmethyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((6-methylpyridin-3-yl)methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((2-methylpyridin-3-yl)methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((pyrazin-2-ylmethyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((5-methylpyridin-3-yl)methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((pyridin-3-ylmethyl)amino)pyridazin-3(2H)-one,
4-(((5,6-dimethylpyridin-2-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-pyridazin-3(2H)-one,
4-(((3-fluoro-6-methyl-pyridin-2-yl)methyl)-amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methylpyridazin-3(2H)one,
4-(((3,6-dimethylpyridin-2-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-(((5-methylpyridin-2-yl)-methyl)amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((3-methyl-pyridin-2-yl)methyl)-amino)pyridazin-3(2H)one,
4-(((5-fluoro-6-methyl-pyridin2yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-pyridazin-3(2H)-one,
4-(((5-chloro-6-methyl-pyridin-2-yl)methyl)-amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-(((6-methylpyridazin-3-yl)methyl)amino)pyridazin-3(2H)-one,
4-((1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl)-methoxy)-2-methyl-pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-((pyrazolo[1,5-a]pyridin-3-ylmethyl)amino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-((pyrazolo[1,5-a]pyridin-3-ylmethyl)amino)-pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-((pyrazolo[1,5-a]pyridin-3-ylmethyl)amino)-pyridazin-3(2H)-one,
4-(((5-(dimethylamino)-1-methyl-1H-pyrazol-4-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(((5-(dimethylamino)-1-methyl-1H-pyrazol-4-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(((5-(dimethylamino)-1-methyl-1H-pyrazol-4-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-(((1,4-dimethyl-1H-pyrazol-5-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-(((1,4-dimethyl-1H-pyrazol-5-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-(((1,4-dimethyl-1H-pyrazol-5-yl)methyl)amino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((5-methylisoxazol-3-yl)methyl)amino)pyridazin-3(2H)-one,
4-(((1,3-dimethyl-1H-1,2,4-triazol-5-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((3-methylisoxazol-5-yl)methyl)amino)pyridazin-3(2H)-one,
4-(((1,4-dimethyl-1H-pyrazol-3-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-(bis((2,6-dimethylpyridin-3-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((1-methyl-1H-pyrazol-3-yl)methyl)-amino)pyridazin-3(2H)one,
2-methyl-4-(((1-methyl-1H-pyrazol-3-yl)methyl)-amino)-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclo-propyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-(((1-methyl-1H-pyrazol-3-yl)methyl)amino)-pyridazin-3(2H)-one,
5-chloro-N-(6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methyl-3-oxo-2,3-dihydro-pyridazin-4-yl)-1-methyl-1Hpyrazole-4carboxamide,
4-(((5-chloro-1-methyl-1H-pyrazol-4-yl)methyl)-amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methyl-4-(((6-methyl-pyridin-2-yl)methyl)-amino)pyridazin-3(2H)one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-4-(((1-methyl-1H-pyrazol-5-yl)methyl)amino)-pyridazin-3(2H)-one,
2-methyl-4-(((1-methyl-1H-pyrazol-5-yl)methyl-)amino)-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclo-propyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methyl-4-(((1-methyl-1H-pyrazol-5-yl)methyl)-amino)pyridazin-3(2H)one,
N-(6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methyl-3-oxo-2,3-dihydropyridazin-4-yl)-1,3-dimethyl-1H-pyrazole-5-carboxamide,
1,3-dimethyl-N-(2-methyl-6-(((1S,2S)-2-(5-methyl-pyridin-2-yl)cyclopropyl-)methoxy)-3-oxo-2,3-dihydropyridazin-4-yl)-1H-pyrazole-5-carboxamide,
1,3-dimethyl-N-(2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)-3-oxo-2,3-dihydropyridazin-4-yl)-1H-pyrazole-5-carboxamide,
2-methyl-4-(((1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl)amino)-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-(((4-methylpyridin-2-yl)methyl)amino)pyridazin-3(2H)-one,
4-(((1-ethyl-1H-pyrazol-3-yl)methyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-((1-(difluoromethyl)-1H-pyrazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)-methylamino)-6-(((1S,2S)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1R,2R)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((2-methylthiazol-5-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((1-methyl-1H-pyrazol-4-yl)methylamino)-pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1R,2R)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-6-(((1R,2R)-2-(1-methyl-1H-indazol-3-yl)cyclopropyl)methoxy)-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-((1,3-dimethyl-1H-pyrazol-5-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methyl-amino)-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclo-propyl)methoxy)-4-((5-methylthiazol-2-yl)methyl-amino)pyridazin-3(2H)one,
2-methyl-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclo-propyl)methoxy)-4-(pyridin-2-ylmethylamino-)pyridazin-3(2H)-one,
2-methyl-6-(((1S,2S)-2-(6-methylpyridin-2-yl)cyclo-propyl)methoxy)-4-(pyridin-3-ylmethylamino-)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta-[b]pyridin-2-yl)cyclop-ropyl)methoxy)-4-((1,3-dimethyl-1H-pyrazol-5-yl)methylamino)-2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta-[b]pyridin-2-yl)cyclo-propyl)-methoxy)-2-methyl-4-((2-methylthiazol-5-yl)methyl-amino)pyridazin-3(2H)one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta-[b]pyridin-2-yl)cyclo-propyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thia-diazol-2-yl)methylamino)-pyridazin-3(2H)-one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methylthiazol-2-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyridazin-3(2H)-one,
4-((4,5-dimethylthiazol-2-yl)methylamino)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-pyridazin-3(2H)-one,
4-((4,5-dimethylthiazol-2-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(5-methyl-pyridin-2-yl)cyclopropyl-)methoxy)pyridazin-3(2H)-one,
4-((4,5-dimethylthiazol-2-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclop-ropyl)methoxy)pyridazin-3(2H)-one,
4-((1,5-dimethyl-1H-pyrazol-3-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-((5-methylthiazol-2-yl)-methylamino-)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyridazin-3(2H)-one,
4-((1,3-dimethyl-1H-pyrazol-5-yl)methyl-amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methylpyridazin-3(2H)one,
4-(4-methoxybenzyl-amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)-cyclopropyl)methoxy)-2-methylpyridazin-3(2H)one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)-cyclopropyl-)methoxy)-2-methyl-4-(pyridin-2-yl-methyl-amino)pyridazin-3(2H)one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-(pyridin-3-ylmethylamino-)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-2-methyl-4-(2-(thiazol-2-yl)ethylamino-)pyridazin-3(2H)-one,
4-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
4-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-2-methyl-6-(((1S,2S)-2-(1-methyl-1H-pyrazol-3-yl)cyclopropyl)methoxy)pyridazin-3(2H)-one,
5-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methyl-amino)pyridazin-3(2H)-one,
5-chloro-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-(4-methoxybenzyl)-6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)cyclopropyl-)methoxy)-4-((5-methyl-1,3,4-thiadiazol-2-yl)methyl-amino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
2-ethyl-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-4-((5-methyl-1,3,4-thiadiazol-2-yl)methylamino)pyridazin-3(2H)-one,
4-((4-methoxybenzyl)(prop-2-ynyl)amino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
4-((1H-1,2,3-triazol-4-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxy-pyridin-2-yl)-cyclopropyl-)methoxy)-2-methyl-4-((1-methyl-1H-1,2,3-triazol-4-yl)methylamino)pyridazin-3(2H)-one,
6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methyl-4-((2-methyl-2H-1,2,3-triazol-4-yl)methylamino)pyridazin-3(2H)-one
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.
16. A method for treating schizophrenia in a human patient in need thereof which comprises administering to the patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.