Camptothecin derivatives with antitumor activity

Compounds of general formula (I):

• wherein:
• R is alkyl, aminoalkyl, hydroxyalkyl, nitrile, alkoxymino, aryloxymino, silylalkyl;
• R1 is hydrogen, hydroxy, alkoxy, aminoalkyl;
• R2 is hydrogen, hydroxy, alkoxy, aminoalkyl, optionally protected hydroxyl;
• wherein the alkyl, alkoxy, aminoalkyl or alkoxymino groups can contain 1 to 8 carbon atoms, in a straight or branched chain, whereas the aryloxymino group can contain 5 to 10 carbon atoms;
• the pharmaceutically acceptable salts, isomers, enantiomers, diastereomers thereof and corresponding mixtures, which is selected from the group consisting of:
• a) 4,5-dihydro-triazole[5,4-c]16a-deoxocamptothecin, and
• b) triazole[5,4-c]16a-deoxocamptothecin.

A process for the preparation of the compounds of formula (I), which process substantially comprises steps (a)-(e) shown in the following scheme:

• wherein:
• a) protection of precursor hydroxy groups;
• b) derivatization at 5- with N,N-diprotected hydrazine;
• c) optional conversion of the pyridone ring to thiopyridone ring;
• d) removal of the protective groups with concomitant cyclization;
• e) optional aromatization of the pyrazole ring;
• and wherein R is alkyl, aminoalkyl, hydroxyalkyl, nitrile, alkoxymino, aryloxymino, silylalkyl;
• R1 is hydrogen, hydroxy, alkoxy, aminoalkyl;
• R2 is hydrogen, hydroxy, alkoxy, aminoalkyl, optionally protected hydroxyl;
• while PG is a hydroxy-protective group.