A new family of water-soluble, third generation antitumor platinum complexes.
[1,1-Cyclobutanedicarboxylato(2)-O,O'](1,3-dioxane-5,5-dimethan amine- N,N')platinum(II), 3a, a third generation, very water-soluble platinum complex, has been synthesized along with several of its analogues. All members of the new family contain a 1,3-dioxane or 1,3-dioxolane-1,3-diamine as their basic ligand, a moiety which contributes to their increased water solubility, and a bidentate acid ligand, which is responsible for their good stability. They were all easily crystallized and characterized by 1H NMR and elemental analysis, and the parent complex 3a was further characterized by 13C NMR. Their very desirable physical properties combined with their broad spectrum of antitumor activity and reduced toxicity make them good candidates of further development.
Bitha
P
P
American Cyanamid Company, Medical Research Division, Pearl River, New York 10965.
Carvajal
S G
SG
Citarella
R V
RV
Delos Santos
E F
EF
Durr
F E
FE
Hlavka
J J
JJ
Lang
S A
SA
Lindsay
H L
HL
Thomas
J P
JP
Wallace
R E
RE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D016190:Carboplatin; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000627:therapeutic use; D004146:Dioxanes / Q000138:chemical synthesis* / Q000627:therapeutic use; D004147:Dioxins / Q000138:chemical synthesis*; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000627:therapeutic use; D004149:Dioxoles / Q000138:chemical synthesis*; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012995:Solubility; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004146:Dioxanes; D004147:Dioxins; D004148:Dioxolanes; D004149:Dioxoles; D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin