Nitrocatechol derivatives as COMT inhibitors
New compounds of formula I are described. The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders.
1. A compound according to formula IVA, IVB or IVC
wherein
R 4 , R 5 , R 6 and R 7 independently from each other represent hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -thioalkyl, C 1 -C 6 -alkoxy, C 6 -C 12 -aryloxy or a C 6 -C 12 -thioaryl group, C 1 -C 6 -alkanoyl or C 7 -C 13 -aroyl group, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 3 -C 12 -cycloalkylamino or C 3 -C 12 -heterocycloalkylamino, C 1 -C 6 -alkylsulphonyl or C 6 -C 12 -arylsulphonyl, halogen, C 1 -C 6 -haloalkyl, trifluoromethyl, cyano, nitro or a heteroaryl group; and
R 8 and R 9 independently from each other represent hydrogen or suitable protective groups for aromatic hydroxyl groups.
2. A compound according to claim 1 wherein the suitable protective groups for aromatic hydroxyl groups are selected from methyl, ethyl, isopropyl, benzyl, 4-methoxybenzyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, tetrahydropyranyl, phenacyl, allyl, trimethylsilyl, tert-butyldimethylsilyl, benzyloxycarbonyl, tert-butoxycarbonyl, ester, sulphonate, carbamate, phosphinate, acetal and ketal derivatives.
3. A compound according to claim 1 , wherein one of the groups R 8 and R 9 is hydrogen and the other is methyl.
4. A compound according to claim 1 , wherein R 8 represents methyl and R 9 represents hydrogen.
5. A compound according to formula VIA, VIB or VIC
wherein
R 4 , R 5 , R 6 and R 7 independently from each other represent hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -thioalkyl, C 1 -C 6 -alkoxy, C 6 -C 12 -aryloxy or a C 6 -C 12 -thioaryl group, C 1 -C 6 -alkanoyl or C 7 -C 13 -aroyl group, amino, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 3 -C 12 -cycloalkylamino or C 3 -C 12 -heterocycloalkylamino, C 1 -C 6 -alkylsulphonyl or C 6 -C 12 -arylsulphonyl, halogen, C 1 -C 6 -haloalkyl, trifluoromethyl, cyano, nitro or a heteroaryl group; and
R 8 and R 9 independently from each other represent hydrogen or suitable protective groups for aromatic hydroxyl groups.
6. A compound according to claim 5 wherein the suitable protective groups for aromatic hydroxyl groups are selected from methyl, ethyl, isopropyl, benzyl, 4-methoxybenzyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, tetrahydropyranyl, phenacyl, allyl, trimethylsilyl, tert-butyldimethylsilyl, benzyloxycarbonyl, tert-butoxycarbonyl, ester, sulphonate, carbamate, phosphinate, acetal and ketal derivatives.
7. A compound according to claim 5 wherein one of the groups R 8 and R 9 is hydrogen and the other is methyl.
8. A compound according to claim 5 wherein R 8 represents methyl and R 9 represents hydrogen.