Pyrazolo[3,4-c]pyridines as gsk-3 inhibitors
The present invention relates to novel compounds, in particular to novel pyrazolopyridine derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds in medicine.
1. A compound of formula (I):
or a derivative thereof,
wherein;
R 1 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclyl and the alkyl moieties may each independently be unsubstituted or substituted; and
R 2 is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl.
2. The compound as claimed in claim 1 wherein R1 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclyl and the alkyl moieties may each independently be unsubstituted or substituted; and
wherein R 2 is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl.
3. A compound of formula (IA),
or a derivative thereof,
wherein;
R 1 is C 1-6 alkyl, cycloC 3-8 alkyl, di(C 1-6 alkyl)aminoalkyl, phenyl optionally substituted by di(C 1-6 alkyl)amino, heterocyclyl wherein the heterocyclyl moiety may be optionally substituted by C 1-6 alkyl and heterocyclylC 1-6 alkyl wherein the heterocyclyl moiety may be optionally substituted by C 1-6 alkyl and phenyl; and
R 2 is phenyl optionally substituted by one or more halo atoms, quinolinyl and pyridinyl optionally susbtituted by C 1-6 alkyl, C 1-6 alkoxy and phenyl.
4. The compound as claimed in claim 1 , wherein R 1 is n-propyl, iso-propyl, cyclopropyl, cyclopentyl, 3-dimethylaminopropyl, 4-dimethylaminophenyl, 3-(pyrrolidin-1-yl)propyl, 3-(piperidin-1-yl)propyl, 3-(4-ethylpiperazin-1-yl)propyl, 1-methylpiperidin-4-yl and 4-[(pyrrolidin-1-yl)methyl]phenyl and wherein R 2 is as defined in claim 1 .
5. The compound as claimed in claim 1 , wherein R 1 is as defined in claim 1 and wherein R 2 is phenyl, 2-chlorophenyl, 2,3-difluorophenyl, 4-fluorophenyl, 2,3,4-trifluorophenyl, pyridin-3-yl, 5-phenylpyridin-3-yl, 6-methylpyridin-3-yl, 6-methoxypyridin-3-yl and quinolin-3-yl.
6. The compound as claimed in claim 1 , wherein R 1 is n-propyl, iso-propyl, cyclopropyl, cyclopentyl, 3-dimethylaminopropyl, 4-dimethylaminophenyl, 3-(pyrrolidin-1-yl)propyl, 3-(piperidin-1-yl)propyl, 3-(4-ethylpiperazin-1-yl)propyl, 1-methylpiperidin-4-yl and 4-[(pyrrolidin-1-yl)methyl]phenyl and wherein R 2 is phenyl, 2-chlorophenyl, 2,3-difluorophenyl, 4-fluorophenyl, 2,3,4-trifluorophenyl, pyridin-3-yl, 5-phenylpyridin-3-yl, 6-methylpyridin-3-yl, 6-methoxypyridin-3-yl and quinolin-3-yl.
7. A pharmaceutical composition which comprises a compound as claimed in claim 1 or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier.
8. A process for the preparation of a compound as claimed in claim 1 or a derivative thereof, which process comprises reaction of a compound of formula (II),
wherein;
R 2 is as defined in formula (I), with a compound of formula (III),
wherein;
R 1 is as defined in formula (I) and X is a leaving group, and thereafter, if required, carrying out one or more of the following optional steps:
(i) converting a compound of formula (I) to a further compound of formula (I);
(ii) removing any necessary protecting group;
(iii) preparing an appropriate derivative of the compound so formed.
9. A process for the preparation of a compound as claimed in claim 1 or a derivative thereof, which process comprises reaction of a compound of formula (V),
wherein;
R 1 and R 2 are as defined in formula (I), with a nucleophile, and thereafter, if required, carrying out one or more of the following optional steps:
(i) converting a compound of formula (I) to a further compound of formula (I);
(ii) removing any necessary protecting group;
(iii) preparing an appropriate derivative of the compound so formed.
10. The compound as claimed in claim 3 , wherein R 1 is n-propyl, iso-propyl, cyclopropyl, cyclopentyl, 3-dimethylaminopropyl, 4-dimethylaminophenyl, 3-(pyrrolidin-1-yl)propyl, 3-(piperidin-1-yl)propyl, 3-(4-ethylpiperazin-1-yl)propyl, 1-methylpiperidin-4-yl and 4-[(pyrrolidin-1-yl)methyl]phenyl and wherein R 2 is as defined in claim 3 .
11. The compound as claimed in claim 3 , wherein R 1 is as defined in claim 3 and wherein R 2 is phenyl, 2-chiorophenyl, 2,3-difluorophenyl, 4-fluorophenyl, 2,3,4-trifluorophenyl, pyridin-3-yl, 5-phenylpyridin-3-yl, 6-methylpyridin-3-yl, 6-methoxypyridin-3-yl and quinolin-3-yl.
12. The compound as claimed in claim 3 , wherein R 1 is n-propyl, iso-propyl, cyclopropyl, cyclopentyl, 3-dimethylaminopropyl, 4-dimethylaminophenyl, 3-(pyrrolidin-1-yl)propyl, 3-(piperidin-1-yl)propyl, 3-(4-ethylpiperazin-1-yl)propyl, 1-methylpiperidin-4-yl and 4-[(pyrrolidin-1-yl)methyl]phenyl and wherein R 2 is phenyl, 2-chlorophenyl, 2,3-difluorophenyl, 4-fluorophenyl, 2,3,4-trifluorophenyl, pyridin-3-yl, 5-phenylpyridin-3-yl, 6-methylpyridin-3-yl, 6-methoxypyridin-3-yl and quinolin-3-yl.