8-hydroxy quinoline derivatives
The present invention relates to a method for the treatment, amelioration and/or prophylaxis of a neurological condition, in particular neurodegenerative disorders which comprises the administration of an effective amount of a compound of formula (I): to a subject in need thereof. The present invention also relates to a compound of formula (II) and processes for its preparation.
1. A compound of the formula
or pharmaceutically acceptable salts, thereof in which
R 1 is H;
R 2 is; optionally substituted phenyl; optionally substituted naphthyl; optionally substituted tetrahydronaphthyl; optionally substituted biphenyl; optionally substituted heterocyclyl; COR 6 ; CSR 6 ; CN; (CH 2 )NR 9 R 10 ; HCNOR 9 ; HCNNR 9 R 10 ; OR 11 ; SR 11 ; NR 11 R 12 or SO 2 NR 13 R 14 ;
R 6 is H, C 1-6 alkyl, optionally substituted C 2-6 alkenyl, hydroxy, optionally substituted aryl, optionally substituted heterocyclyl, SR 7 or NR 7 R 8 ;
R 7 and R 8 are either the same or different and selected from H, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted aryl and optionally substituted heterocyclyl;
R 9 is H, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted aryl or optionally substituted heterocyclyl;
R 10 is hydrogen, methyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted C 2-6 alkenyl, optionally substituted aryl or optionally substituted heterocyclyl;
R 11 is H, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted aryl or optionally substituted heterocyclyl or together with R 12 form optionally substituted heterocyclyl;
R 12 is optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted aryl or optionally substituted heterocyclyl or together with R 11 form optionally substituted heterocyclyl;
R 3 , R and R′ are either the same or different and selected from H, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 1-6 alkoxy, optionally substituted acyl, hydroxy, optionally substituted amino, optionally substituted thio, optionally substituted sulphonyl, optionally substituted sulphinyl, optionally substituted sulphonylamino, halo, SO 3 H, amine, CN, CF 3 , optionally substituted aryl and optionally substituted heterocyclyl; and
R 4 and R 5 are chloro,
wherein the optional substituent is C 1-6 alkyl, CF 3 , fluorine, chlorine, iodine, cyano, C 1-6 alkoxy, 5 or 6-membered aryl, heteroaryl, amino or C 1-6 alkylamino.
2. The compound according to claim 1 in which either R 2 is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted tetrahydronapthyl, optionally substituted biphenyl, optionally substituted heterocyclyl, CH 2 NR 9 R 10 or COR 6 or at least one of R, R 3 and R′ is optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted heterocyclyl, CH 2 NR 9 R 10 or COR 6 in which R 6 is NR 7 R 8 or NR 11 R 12 .
3. A compound of the formula
or pharmaceutically acceptable salts, thereof.
4. The compound according to claim 3 having the formula
or pharmaceutically acceptable salts, thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of a compound according any one of claims 1 , 3 or 4 in association with a pharmaceutically acceptable carrier.
6. The pharmaceutical composition according to claim 5 which additionally comprises a medicament, said medicament being an inhibitor of the acetyl cholinesterase active site, an antioxidant, an anti-inflammatory agent or an estrogenic agent.
7. A hydrate of the compound of claim 1 .
8. A hydrate of the compound of claim 3 .
9. A hydrate of the compound of claim 4 .