Orally active docetaxel analogue: synthesis of 10-deoxy-10-C-morpholinoethyl docetaxel analogues.
To improve cytotoxicity of 10-deoxy-10-C-morpholinoethyl docetaxel analogues against various tumor cell lines including resistant cells expressing P-glycoprotein (P-gp), we modified the 7-hydroxyl group to hydrophobic groups (methoxy, deoxy, 6,7-olefin, alpha-F, 7-beta-8-beta-methano, fluoromethoxy). Among these analogues, the 7-methoxy analogue showed the strongest cytotoxicity. This analogue showed potent activity against B16 melanoma BL6 in vivo by oral administration.
Iimura
S
S
New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Uoto
K
K
Ohsuki
S
S
Chiba
J
J
Yoshino
T
T
Iwahana
M
M
Jimbo
T
T
Terasawa
H
H
Soga
T
T
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D015996:Survival Rate; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects
C427063:10-deoxy-10-C-morpholinoethyl docetaxel; D000972:Antineoplastic Agents, Phytogenic; D009025:Morpholines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel