| 摘要 |
900312 RV6 SHAL3.0-007 There are disclosed two, cytotoxic, structurally closely related groups of compounds, namely compounds of the formula: wherein R1 is L or D-Phe, D-Trp, L or D-Mel, R3 is Mel, Tyr or Phe, R6 is Thr or Val, R8 is Thr, Trp or Mel, Q is selected from the group consisting of hydrogen, L and D-Mel, Mel-Mel dipeptide, cyclopropanealkanoyl, aziridine-2-carbonyl, methotrexoyl, 1,4naphthoquinone-5-oxycarbonylethyl, epoxyalkyl and the n-carbonyl-alkylamino derivatives thereof; and the n-carbonyl-alkanoyl derivatives of 2-hydroxymethyl-anthraquinone, doxorubicin, esperamycin, and mitomycin C; wherein the ncarbonyl-alkylamino group has the formula -CO-(CH2)n-NH- where n is 2-6, and then-carbonyl-alkanoyl group has the formula -CO-(CH2)n-CO- where n is 2-6, and compounds of formula wherein R1 is L or D-Phe, L or D-Trp, R3 is Phe or Tyr, R5 is Val or Thr, R8 is Thr or Trp, A is a diaminoacyl residue having the formula -HNCH2-(CH2)m-CH(NH)-(CH2)n-CO- where m is 0 or 1 and n is 0 or 1, Q1 is a cytotoxic moiety having the formula Q2 or (B)2Q3 or (Q4)2 wherein Q2 is Pt(Y)2, where Y is an anion of pharmaceuticaliy acceptable acid, Q3 is a non-platinum-group metal, selected from the group consisting of titanium, vanadium, iron, copper, cobalt, gold, nickel, cadmium and zinc, Q4 is selected from the group consisting of L or D-Mel, Mel-Mel dipeptide, cyclopropanealkanoyl, aziridine-2-carbonyl, epoxyalkyl, 1,4-naphthoquinone-5-oxycarbonylethyl or the .OMEGA.-carbonyl-alkylamino derivatives thereof; the .OMEGA.-carbonyl-alkanoyl derivatives of 2-hydroxymethyl-anthraquinone, doxorubicin, esperamycin and mitomycin C, wherein the .OMEGA.-carbonyl-alkylamino group has the formula -CO-(CH2)n-NH- where n is 2-6 and the .OMEGA.-carbonyl-alkanoyl group has the formula -CO-(CH2)n-CO- where n is 2-6, B is a substituted aralkylidene or heteroaralkylidene selected from the group consisting of halo and nitrophenyl lower-alkylidenes; lower alkyl hydroxymethyl or phosphoxymethyl pyridyl lower alkylidenes, wherein lower alkmeans 1-6 carbon atoms and the salts thereof with pharmaceutically acceptable acids and bases.
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