Patent EA-003333-B1 (EA)
Title: Amino anthracyclinone derivatives and their use in the treatment of amyloidosis
Inventor: BANDIERA TIZIANO
IPC: A61P25/28
Filed: 1999-02-25
Abstract: 1. A compound of formula 1, wherein R1 represents: hydrogen, hydroxy, a group of formula OR7 wherein R7 is C1-C6 alkyl, C2-C6 alkenyl; R2 represents: hydrogen, hydroxy, diethylamino, piperidino, tetrahydropyridino or morpholino; and either R3, taken alone, represents hydrogen or hydroxy, and R4 and R5, when taken alone, independently represent hydrogen, hydroxy or, taken together with the carbon atom, represent a carbonyl group; or R3 and R4, taken together, represent a group of formula wherein R8 and R9 represent a C1-C6 alkyl and R5 represents hydrogen; R6 represents: hydrogen or a phenyl group, optionally substituted by methyl, methoxy or halogen, and the pharmaceutically acceptable salt thereof. 2. A compound according to claim 1, characterized in that R1 represents: hydrogen, hydroxy or methoxy; R2 represents: hydrogen, hydroxy or morpholino; R3 represents hydroxy; R4, taken alone, represents hydroxy; R5, taken alone, represents hydrogen or R4 and R5 taken together with the carbon atom represent a carbonyl group; R6 represents hydrogen, and the pharmaceutically acceptable salt thereof. 3. A compound according to claim 1, which is 14-(1,2,3,6-tetrahydropyridin-1-yl)daunomycinone, or a pharmaceutically acceptable salt thereof. 4. A process for preparing a compound of formula 1, as defined in claim 1, which process comprises: (a) reacting a compound of formula 2, wherein R1 and R3 are as defined in claim 1 and R2 is hydrogen or hydroxy, with a compound of formula 3, wherein R6 is as defined in claim 1, and (b) converting a compound of formula 1 as defined above into a different compound of formula 1 by appropriate chemical reactions, and/or if desired, converting the resulting compound of formula 1 into a pharmaceutically acceptable salt thereof. 5. A process according to claim 4, wherein in step (a) a compound of formula 2 as defined in claim 4 is reacted with a compound of formula 3 as defined in claim 4 in a proper organic solvent at a temperature ranging from -10 degree C. to room temperature and for a period of from 6 to 48 hours. 6. A pharmaceutical composition which comprises, as active ingredient, a compound of formula 1 as defined in any of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent. 7. A compound of formula 1 as defined in any of claims 1 to 3, or a pharmaceutically acceptable salt thereof, for use in the treatment of the human or animal body. 8. Use of a compound of formula 1 as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of AL amyloidosis, Alzheimer's disease or Down's syndrome. 9. A method of treating a human or animal suffering from, or susceptible to, an amyloidois disease, which method comprises administering thereto a non-toxic and effective amount of a compound of formula (I), as defined in any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof.