| 摘要 |
1- or 2- or 7-(substituted)-3-(optionally hetero)arylamino-[1H,2H]-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione derivatives, in free, salt or prodrug form, are useful as pharmaceuticals, particularly as phosphodiesterase 1 inhibitors, useful for the treatment of diseases involving disorders of the dopamine D1 receptor intracellular pathway, such as Parkinson's disease, depression, narcolepsy and damage to cognitive function, e.g., in schizophrenia or disorders that may be ameliorated through enhanced progesterone—signaling pathway, e.g., female sexual dysfunction. |
| 主权项 |
1. A compound of formula Q:wherein
(i) R1 is H or C1-6alkyl; (ii) R2 is
H,C1-6 alkyl,C3-8 cycloalkyl optionally substituted with one or more amino,C3-8heterocycloalkyl optionally substituted with C1-6alkyl,C3-8cycloalkyl-C1-6alkyl,C1-6haloalkyl,C0-6alkylaminoC0-6alkyl,hydroxyC1-6alkyl,arylC0-6alkyl,heteroarylalkyl,C1-6alkoxyarylC1-6alkyl, or-G-J wherein:
G is a single bond or, alkylene;J is cycloalkyl or heterocycloalkyl optionally substituted with alkyl; (iii) R3 is
a) D-E-F wherein
1. D is single bond, C1-6alkylene, or arylC1-6alkylene;2. E is a C1-6alkylene, arylene, C1-6alkylarylene, aminoC1-6alkylene or amino; and3. F is
C1-6alkyl,aryl,heteroaryl optionally substituted with C1-6alkyl,heteroC3-8cycloalkyl optionally substituted with C1-6alkyl,aminoC1-6alkoxy, or—O-haloC1-6alkylb) R3 is a substituted heteroarylalkyl,c) R3 is attached to one of the nitrogen atoms on the pyrazolo portion of Formula I and is a moiety of Formula A wherein X, Y and Z are, independently, N or C, and R8, R9, R11 and R12 are independently H or halogen; and R10 is halogen, C1-6alkyl, C3-8cycloalkyl, C1-6haloalkyl, aryl, heteroaryl, (iv) R4 is aryl (e.g., phenyl) optionally substituted with one or more halo, hydroxyl or C1-6alkoxy, heteroaryl or heteroC3-6 cycloalkyl; and (v) R5 is H, C1-6alkyl, C3-8 cycloalkyl, heteroaryl, aryl, or p-benzylaryl;wherein “alk”, “alkyl”, “haloalkyl” or “alkoxy” refers to C1-6 alkyl and “cycloalkyl” refers to C3-8cycloalkyl;in free or salt form. |
