| abstract |
The present invention relates to novel prodrug forms of ribonucleoside diphosphate reductase inhibitors 3-aminopyri-dine-2-carboxaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) which have increased water solubility, bioavailability and resistance to in vivo acetylation of their amino functions. Novel compounds according to the present invention relate to those of formula (1), where R4 is H or CH3 and R5 is CHR, benzyl or ortho or para substituted benzyl; R is H, CH3, CH2CH3, CH2CH2CH3 or (a); R' is a free acid phosphate, phosphate salt or an -S-S-R" group; R" is CH2CH2NHR6, CH2CH2OH, CH2COOR7, an ortho or para substituted alkylphenyl and ortho or para substituted nitro-phenyl; R6 is H, C1-C4 acyl group, trifluoroacetyl, benzoyl or substituted benzoyl group, and R7 is H, C1-C4 alkyl or a benzyl or substituted benzyl. |