Substituted pyrazolo[3,4-d]pyrimidin-4-one compounds as phosphodiesterase inhibitors
The invention relates to novel alkyl-substituted pyrazolopyrimidines, process for their preparation, and the use thereof for producing medicaments for improving perception, concentration, learning and/or memory with compounds of formula (I):
1. A compound of the formula
in which
R 1 is C 1 -C 6 -alkyl, trifluoromethyl, hydroxy, C 1 -C 6 -alkoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , where C 1 -C 6 -alkyl is optionally substituted by 1 to 3 radicals independently of one another selected from the group of hydroxy, C 1 -C 6 -alkoxy, halogen, trifluoromethyl, trifluoromethoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , and
R 5 is C 1 -C 6 -alkyl,
R 6 and R 7 are independently of one another hydrogen, C 6 -C 10 -aryl, C 1 -C 6 -alkyl, or
together with the nitrogen atom to which they are bonded form a 4- to 10-membered heterocyclyl,
R 2 is hydrogen, C 1 -C 6 -alkyl, trifluoromethyl, C 1 -C 6 -alkoxy,
or
R 1 and R 2 together with the carbon atom to which they are bonded form C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkenyl or 4- to 10-membered heterocyclyl, which are optionally substituted by up to 2 substituents from the group of C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, oxo, —C(═O)OR 8 , and
R 8 is C 1 -C 6 -alkyl or benzyl,
provided that, when R 1 is C 1 -C 6 -alkyl, R 2 is not hydrogen or C 1 -C 6 -alkyl,
R 3 is hydrogen or C 1 -C 6 -alkyl,
R 4 is pentan-3-yl or C 3 -C 6 -cycloalkyl,
X is oxygen or sulfur,
and the salts thereof.
2. A compound as claimed in claim 1 , wherein
R 1 is C 1 -C 6 -alkyl, hydroxy, C 1 -C 6 -alkoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , where C 1 -C 6 -alkyl is optionally substituted by hydroxy, C 1 -C 6 -alkoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , and
R 5 is C 1 -C 6 -alkyl,
R 6 and R 7 are independently of one another hydrogen, C 6 -C 10 -aryl, C 1 -C 6 -alkyl, or together with the nitrogen atom to which they are bonded form a 4- to 10-membered heterocyclyl,
R 2 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy,
or
R 1 and R 2 together with the carbon atom to which they are bonded form C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkenyl or 4- to 10-membered heterocyclyl, which are optionally substituted by up to 2 substituents from the group of C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, oxo, —C(═O)OR 8 , and
R 8 is C 1 -C 6 -alkyl or benzyl,
provided that, when R 1 is C 1 -C 6 -alkyl, R 2 is not hydrogen or C 1 -C 6 -alkyl,
R 3 is hydrogen or C 1 -C 6 -alkyl,
R 4 is pentan-3-yl or C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
and the salts thereof.
3. A compound as claimed in claim 1 , where
R 1 is C 1 -C 4 -alkyl, hydroxy, C 1 -C 4 -alkoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , where C 1 -C 4 -alkyl is optionally substituted by hydroxy, trifluoromethyl, C 1 -C 4 -alkoxy, —C(═O)OR 5 or —C(═O)NR 6 R 7 , and
R 5 is C 1 -C 4 -alkyl,
R 6 and R 7 are independently of one another hydrogen, phenyl, C 1 -C 4 -alkyl, or
together with the nitrogen atom to which they are bonded form a 5- to 6-membered heterocyclyl,
R 2 is hydrogen, C 1 -C 4 -alkyl, trifluoromethyl, C 1 -C 4 -alkoxy,
or
R 1 and R 2 together with the carbon atom to which they are bonded form C 5 -C 6 -cycloalkyl, C 5 -C 6 -cycloalkenyl or 5- to 6-membered heterocyclyl, which are optionally substituted by up to 2 substituents from the group of C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, hydroxy, oxo, —C(═O)OR 8 , and
R 8 is C 1 -C 4 -alkyl or benzyl,
provided that, when R 1 is C 1 -C 4 -alkyl, R 2 is not hydrogen or C 1 -C 4 -alkyl,
R 3 is hydrogen,
R 4 is pentan-3-yl or C 5 -C 6 -cycloalkyl,
X is oxygen or sulfur,
and the salts thereof.
4. A pharmaceutical composition comprising at least one of the compounds as claimed in any one of claims 1 to 3 and at least one pharmaceutically acceptable, essentially nontoxic carrier or excipient.
5. A compound selected from the group consisting of
and the salts thereof.