Substituted pyrazolo[3,4-d]pyrimidines as PDE9 inhibitors
The present invention is directed to pyrazolopyrimidine compounds of the general structural formula I: which may be useful as therapeutic agents for the treatment of disorders associated with phosphodiesterase 9 (PDE9). The present invention also relates to the use of such compounds for treating cardiovascular and cerebrovascular diseases, such as hypertension, chronic kidney disease and heart failure, and 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 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2 , wherein the compound is:
4. The compound of claim 2 , wherein the compound is a pharmaceutically acceptable salt of:
5. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 5 , wherein the compound is:
7. The compound of claim 5 , wherein the compound is a pharmaceutically acceptable salt of:
8. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 8 , wherein the compound is:
10. The compound of claim 8 , wherein the compound is a pharmaceutically acceptable salt of:
11. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 11 , wherein the compound is:
13. The compound of claim 11 , wherein the compound is a pharmaceutically acceptable salt of:
14. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14 , wherein the compound is:
16. The compound of claim 14 , wherein the compound is a pharmaceutically acceptable salt of:
17. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 17 , wherein the compound is:
19. The compound of claim 17 , wherein the compound is a pharmaceutically acceptable salt of:
20. A pharmaceutical composition comprising an inert carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
21. A method for inhibiting phosphodiesterase 9 activity in a mammalian patient, comprising administering to the mammalian patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
22. The method of claim 21 , wherein the mammalian patient has a disease or disorder associated with phosphodiesterase 9 dysfunction.
23. The method of claim 22 , wherein the disease or disorder associated with phosphodiesterase 9 dysfunction is selected from the group consisting of heart failure, hypertension, a cardiovascular disease, a cerebrovascular disease, and a chronic kidney disease.
24. The method of claim 22 , wherein the disease or disorder associated with phosphodiesterase 9 dysfunction is selected from the group consisting of drug induced psychosis, an anxiety disorder, a delusional disorder, a movement disorder, a neurological disorder, and a psychotic disorder.