Improved antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin.
The preparation and antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin are described. Di-N-alkylation of pirarubicin with bis(2-iodoethyl)ether gave 3'-morpholino-pirarubicin, which was converted into its 13-tosylhydrazone, 13-deoxy derivative and 13-(S)- and 13-(R)-dihydro derivatives. Intraperitoneal administration to murine tumors indicated that the effective dose ranges of the compounds having sp3 carbon at C-13 position were broader than those of the compounds having sp2 carbon. By oral administration, 13-(S)-dihydro isomer was more effective than 13-(R)-dihydro isomer.
Ajito
K
K
Institute of Microbial Chemistry, Tokyo, Japan.
Ikeda
D
D
Nosaka
C
C
Komuro
K
K
Kondo
S
S
Takeuchi
T
T
D000284:Administration, Oral; D000818:Animals; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D009025:Morpholines; D004317:Doxorubicin; C027260:pirarubicin