IMINO-AZA-ANTHRACYCLINONE DERIVATIVES FOR THE TREATMENT OF AMYLOIDOSIS

摘要

1. A compound of the formula (1): wherein: R1 is hydrogen, and lower alkyl; R2 is hydrogen, C1-4 alkyl, allyl, benzyl optionally substituted with one-three substituents, selected from the group comprising trifluoromethyl, C1-4 alkyl, C1-4 alkoxy, halo and hydroxy; pyridinomethyl, pyridinomethylcarbonyl; R3 is selected from the groups of hydroxyl, C1-4 alkoxy, benzyloxy, methylamino, or pyridinmethyloxy, 4-morpholinyl, 4-methylpiperazinyl, provided that when R1 is methoxy group and R3 is hydroxy group, R2 differs from 4-pyridinmethyl, or a pharmaceutically acceptable salt thereof. 2. The compound of Claim 1, wherein R1 is selected from hydrogen and methoxy; R2 is hydrogen, methyl, allyl, benzyl, 3-bromobenzyl, 4-trifluoromethylbenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 3,5-di-tert-butyl-4-hydroxybenzyl, pyridinemethyl, nicotinoyl; R3 is hydroxy, methoxy, ethoxy, benzyloxy, 4-pyridenemethyloxy, methylamino, 4-morpholinyl, 4-methylpiperazinyl, or a pharmaceutically acceptable salt thereof. 3. The compound of Claim 1, which is selected from 8-N-(3,4-dimethoxybenzyl) anthrazolone oxime, S-N-allylanthrazolone oxime, O-methyloxime S-N-allylanthrazolone, and anthrazalone O-ethyloxime, or a pharmaceutically acceptable salts thereof. 4. A process for preparing a compound of the formula (1), as defined in Claim 1, which process comprises: (a) reacting a compound of the formula (2) wherein R1 and R2 are as defined in Claim 1, with a compound of the formula: R3-NH2 wherein R3 is as defined in Claim 1, and (b) optionally converting the thus obtained compound of the formula (1) into another compound of the formula (1); and/or (c) optionally converting the compound of the formula (1) to a pharmaceutically acceptable salt thereof. 5. The process of Claim 4, wherein in step (a) a compound of the formula (2) as defined in Claim 4, is reacted with a compound of formula R3-NH2.HA, wherein HA represents an inorganic acid, in an organic solvent in the presence of an organic or inorganic base. 6. A pharmaceutical composition, which comprises, as active ingredient, an effective amount of a compound of the formula (1) as defined in any of Claims 1-3, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent. 7. A compound of the formula (1) as defined in any of Claims 1-3, or a pharmaceutically acceptable salt thereof for treating a human or an animal. 8. A compound of the formula (1) as defined in any of Claims 1-3, or a pharmaceutically acceptable salt thereof for producing a pharmaceutical composition for treating an AL amyloidosis disease, Alzheimer's disease, and Down's syndrome. 9. A method of treating a human or animal suffering from, or susceptible to, an amyloidosis disease, which comprises administering thereto an non-toxic and effective amount of a compound of the formula (1), as defined in any of Claims 1-3, or a pharmaceutically acceptable salt thereof.