Synthesis and antitumor activity of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) daunomycinone derivatives modified at C-3' or C-4'.
As a part of a study to exploit anthracycline glycosides effective against resistant tumor cells, the 3'-O-methyl (3), 4'-O-methyl (4), 3'-deoxy (6), 3'-deoxy-3'-fluoro (7), and 3'-deoxy-3'-iodo (8) derivatives of 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)daunomycinone have been prepared by coupling suitably protected glycosyl bromides with daunomycinone. The doxorubicin-type analog (5) of 4 was also prepared. Among the compounds prepared, 5 showed the highest antitumor activity. Relationships between chemical structures of the synthetic products and antitumor activities, together with the degree of resistance were discussed.
Institute of Bioorganic Chemistry, Kawasaki, Japan.
Y
Y
Takagi
N
N
Kobayashi
M S
MS
Chang
G J
GJ
Lim
T
T
Tsuchiya
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000473:pathology; D007941:Leukemia P388 / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C113446:7-O-(2,6-dideoxy-2-fluoro-4-O-methyltalopyranosyl)adriamycinone; D000903:Antibiotics, Antineoplastic; C049731:7-O-(2,6-dideoxy-2-fluorotalopyranosyl)daunomycinone; D004317:Doxorubicin; D003630:Daunorubicin