Bleomycin derivs. with anti tumour activity - made by reacting demethyl bleomycin with carbonyl cpd. substd. by an electrophilic gp. or atom.

摘要

Bleomycine derivs. of formula (I) (where R = -NH(CH2)3S+(CH3)CH2COR1 in which R1 = an organic gp.) and their metal complexes are new. (I) is prepd. by reacting demethyl bleomycine A2 of formula (I) with R = -NH(CH2)3SCH3, or a metal complex of this, with a cpd. of formula XCH2COR1 in which X = an electrophilic atom or gp., esp. Br. Pref. R1 may be bound to the CO gp. via. N, O, S or C atoms, e.g. where R1 = -NR2R3 where R2 and R3 independently = H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, aryl, aralkyl, aralkenyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocycloylalkyl, or R2 and R3 may complete a heterocyclic ring which is opt. substd. and which may contain further heteroatoms chosen from N, S and O, and which contain condensed aryl, heteroaryl and heterocyclyl gps.; or R1 = -OR2, -CH2R2, -CHR2R3, -C(OH)R2R3, -C(NH2)R2R3, in which R2 and R3 are as above, or -CR2R3R4 in which R2, R2 and R4 are as for R2 or R2+R3+R4 together with the C complete a satd., unsatd., or partially unsatd. ring which opt. contains one or more heteroatoms and which may be substd. or may carry one or more condensed rings.