Patent EA-003455-B1 (EA)
Title: L-arabino-disaccharides of anthracyclines, processes for their preparation, and pharmaceutical compositions containing them
Inventor: ANIMATI FABIO
IPC: A61P35/00
Filed: 2000-03-08
Abstract: 1. Compounds of general formula (I) and pharmaceutically acceptable salts thereof, where R is OH; R1 is H or OH; R2 is H or OH or NH2 2. The compounds of formula (I) as claimed in claim 1 included in the group consisting of i) 7-O-[2,6-dideoxy-4-O-(2,3,6-trideoxy-3-amino-alpha-L-arabino-hexopyranosyl)-alpha-L-lyxo-hexopyranosyl]-4-demethoxy-doxorubicinone hydrochloride (R = R1 = OH, R2 = NH2); ii) 7-O-[2,3,6-trideoxy-4-O-(2,3,6-trideoxy-3-amino-alpha-L-arabino-hexopyranosyl)-alpha-L-lyxo-hexopyranosyl]-4-demethoxy-doxorubicinone hydrochloride (R=OH, R1=H, R2=NH2); iii) 7-O-[2,6-dideoxy-4-O-(2,6-dideoxy-alpha-L-arabino-hexopyranosyl)-alpha-L-lyxo-hexopyranosyl]-4-demethoxy-doxorubicinone hydrochloride (R = R1 = R2 = OH); iv) 7-O-[2,3,6-trideoxy-4-O-(2,6-dideoxy-alpha-L-arabino-hexopyranosyl)- alpha-L-lyxo-hexopyranosyl)-4-demethoxy-doxorubicinone hydrochloride (R = R2 = OH, R1 = H). 3. Process for the preparation of compounds of general formula (I) where R is OH; R1 is H or OH; R2 is H or OH or NH2 or pharmaceutically acceptable salts thereof, consisting of the following steps: i) condensation of a compound of formula (II) where R3 is the OR4 group, in which R4 is a protective group for an alcoholic function, selected among the acetyl-, dimethylterbutylsilyl or p-methoxyphenyldiphenylmethyl- groups, with a compound of formula (III) where R5 is H or a protected -OH group; R6 is a H group or a protected -OH group or a protected NH2 group; R7 is a protected -OH group, and X is a group selected among a halogen or a p-nitrobenzoyloxy- or a thiophenyl group, giving compounds of formula (IV): where R3, R5, R6, R7 are as defined above; ii) one or more removal reactions of protective groups of OH and/or NH2 groups of the compounds of formula (IV) giving compounds of formula (I), where R, R1, R2 are as defined above; iii) conversion, if any, of the compounds of formula (I) into a pharmaceutically acceptable salt thereof. 4. The process for the preparation of compounds of formula (I) as claimed in claim 1, where R1 and R2 are as defined above and R is the OH group, or their pharmaceutically acceptable salts, consisting of the following steps: i) bromination of the carbon in position of compounds of formula (I) or their pharmaceutically acceptable salts, where R1 and R2 are as defined above and R is H; ii) hydrolysis of the resulting 14-bromo-derivatives giving compounds of formula (I), where R1 and R2 are as defined above and R is the OH group. 5. Pharmaceutical composition containing as active ingredient at least a compound of general formula (I) as claimed in any of claims 1 and 2, or a pharmaceutically acceptable salt thereof, combined with a pharmaceutically acceptable diluent or carrier. 6. Use of compounds of general formula (I) as claimed in any of claims 1 and 2, or their pharmaceutically acceptable salts, for the preparation of pharmaceutical composition. 7. Use according to Claim 6 wherein the pharmaceutical compositions are anticancer agents.