Heteroaromatic phenylimidazole derivatives as PDE10A enzyme inhibitors

1. A method for the treatment of a subject suffering from a psychiatric disorder selected from the group consisting of schizophrenia, schizoaffective disorder, schizophreniform disorder and bipolar disorder, wherein said treatment alleviates or relieves the symptoms or complications of said disorder, delays the progression of said disorder, and/or cures or eliminates said disorder, comprising administering a therapeutically effective amount of:

(A) a compound having the structure I:

 wherein:

HET1 is:

optionally substituted with up to three substituents R2, R3 and R4 individually selected from the group consisting of hydrogen, C 1 -C 6 alkyl; halogen; cyano, halo(C 1 -C 6 )alkyl; aryl, alkoxy and C 1 -C 6 hydroxyalkyl, and wherein * denotes the attachment point;

HET2 is:

(1) a heteroaromatic group of formula III or IV:

 wherein Y can be N, S, O or CH, X can be N or CH, wherein formula III contains 1 or 2 N, 1 S, or 1 O, or 1 N and 1 S and wherein formula IV contains 1 or 2 N; and wherein HET2 may optionally be substituted with up to three substituents R5, R6 and R7 individually selected the group consisting of hydrogen, C 1 -C 6 alkyl; halogen; cyano, halo(C 1 -C 6 )alkyl; aryl, alkoxy and C 1 -C 6 hydroxyalkyl, and wherein * denotes the attachment point; or

(2) a heteroaromatic group of formula:

 that may optionally be substituted with up to three substituents R5, R6 and R7 individually selected the group consisting of hydrogen, C 1 -C 6 alkyl; halogen; cyano, halo(C 1 -C 6 )alkyl; aryl, alkoxy and C 1 -C 6 hydroxyalkyl, and wherein * denotes the attachment point;

-L- is a linker selected from the group consisting of —S—CH 2 —, —CH 2 —S—, —CH 2 —CH 2 —, —CH═CH—, and —C≡C—; and

R 1 is selected from the group consisting of H, C 1 -C 6 alkyl; C 1 -C 6 alkyl(C 3 -C 8 )cycloalkyl; C 1 -C 6 hydroxyalkyl, CH 2 CN, CH 2 C(O)NH 2 , C 1 -C 6 arylalkyl, and C 1 -C 6 alkyl-heterocycloalkyl;

or

(B) a pharmaceutically acceptable acid addition salt thereof.

2. The method of claim 1 , wherein the psychiatric disorder is schizophrenia.

3. The method of claim 2 , wherein the schizophrenia is of the paranoid, disorganized, catatonic, undifferentiated or residual type.

4. The method of claim 2 , wherein the psychiatric disorder is a schizoaffective disorder of the delusional type or the depressive type.

5. The method of claim 1 , wherein the psychiatric disorder is bipolar disorder.

6. The method of claim 1 , wherein the method further comprises administering a therapeutically effective amount of compound I in combination with at least one neuroleptic agent.

7. The method of claim 6 , wherein the neuroleptic agent is selected from the group consisting of sertindole, olanzapine, risperidone, quetiapine, aripiprazole, haloperidol, clozapine, ziprasidone and osanetant.

8. The method of claim 1 , wherein the compound is 5,8-Dimethyl-2-{2-[1-methyl-4-(5-methyl-furan-2-yl)-1H-imidazol-2-yl]-ethyl}-[1,2,4]triazolo[1,5-a]pyrazine.

9. The method of claim 1 , wherein the compound is 5,8-Dimethyl-2-[2-(1-methyl-4-thiophen-2-yl-1H-imidazol-2-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrazine.

10. The method of claim 1 , wherein the compound is 5,8-Dimethyl-2-[2-(1-methyl-4-thiazol-2-yl-1H-imidazol-2-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrazine.

11. The method of claim 1 , wherein the compound is 5,8-Dimethyl-2-[2-(1-methyl-4-pyridin-3-yl-1H-imidazol-2-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrazine.

12. The method of claim 1 , wherein the compound is 2-[2-(4-Furan-3-yl-1-methyl-1H-imidazol-2-yl)-ethyl]-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine.

13. The method of claim 1 , wherein the compound is 5,8-Dimethyl-2-[2-(1-methyl-4-thiazol-5-yl-1H-imidazol-2-yl)-ethyl]-[1,2,4]triazolo[1,5-a]pyrazine.