Phenyl-substituted pyrazolopyrimidines
The invention relates to novel phenyl-substituted pyrazolopyrimidines, process for their preparation, and their use for producing medicaments for improving perception, concentration, learning and/or memory.
1. A compound of the formula
in which
R 1 is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy,
R 2 is C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof.
2. A compound as claimed in claim 1 , where
R 1 is phenyl which is substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, chlorine, bromine, C 1 -C 4 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 4 -alkoxy,
R 2 is C 5 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof.
3. A compound as claimed in claim 1 of the formula
in which
R 3 is hydrogen or chlorine,
R 4 is fluorine, chlorine, bromine, methyl, trifluoromethyl,
R 2 is cyclopentyl,
X is oxygen or sulfur,
or a salt thereof.
4. A compound as claimed in claim 1 of the formula (Ia), where
R 3 is hydrogen or chlorine,
R 4 is fluorine, chlorine, bromine, methyl, trifluoromethyl,
R 2 is cyclopentyl,
X is oxygen,
or a salt thereof.
5. A process for preparing a compound of the formula (I):
in which
R 1 is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy,
R 2 is pentan-3-yl or C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof,
wherein
[A] a compound of the formula
in which
R 2 has the meanings indicated,
is converted by reaction with a compound of the formula
R 1 —CH 2 —C(O)—Z (IIIa),
in which
R 1 has the meanings indicated,
and
Z is chlorine or bromine,
initially in the presence of a base into a compound of the formula
in which
R 1 and R 2 have the meanings indicated,
then cyclized in the presence of a base to a compound of the formula
in which
R 1 and R 2 have the meanings indicated,
or
[B] a compound of the formula (II) is reacted with direct cyclization to (Ib) with a compound of the formula
R 1 —CH 2 —C(O)—OR 5 (IIIb),
in which
R 1 has the meanings indicated,
and
R 5 is methyl or ethyl,
in the presence of a base,
or
[C] a compound of the formula
in which
R 2 has the meanings indicated,
is converted initially by reaction with a compound of the formula (IIIa) in the presence of a base into a compound of the formula
in which
R 1 and R 2 have the meanings indicated,
and the latter are cyclized in a second step in the presence of a base and of an oxidizing agent to (Ib),
and a compound of the formula (Ib) is then converted where appropriate by reaction with a sulfurizing agent into the thiono derivatives of the formula
in which
R 1 and R 2 have the meanings indicated,
and the resulting compound of the formula (I) is optionally reacted with the appropriate bases or acids to give a salt thereof.
6. A medicament comprising at least one of the compounds as claimed in any one of claims 1 to 4 and at least one pharmaceutically acceptable, essentially non-toxic carrier or excipient.
7. A method for treating an impairment of learning and/or memory which is a consequence of Alzheimer's disease comprising administering to a human or animal an effective amount of a compound of the formula (I):
in which
R 1 is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy,
R 2 is pentan-3-yl or C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof.
8. The process of claim 5 , wherein the sulfurizing agent is diphosphorus pentasulfide.
9. A method for producing a medicament useful for improving perception, concentration, learning and/or memory comprising formulating a compound of formula (I) together with at least one pharmaceutically acceptable excipient:
in which
R 1 is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy,
R 2 is C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof,
in a form useful for improving perception, concentration, learning and/or memory in a human or animal.
10. A pharmaceutical composition comprising a compound of the formula (I):
in which
R 1 is phenyl which is substituted by 1 to 5 substituents independently of one another selected from the group of halogen, C 1 -C 6 -alkyl, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, nitro and C 1 -C 6 -alkoxy,
R 2 is C 4 -C 6 -cycloalkyl,
X is oxygen or sulfur,
or a salt thereof, as the active moiety,
together with at least one pharmaceutically acceptable excipient.