New highly active taxoids from 9beta-dihydrobaccatin-9,10-acetals. Part 3.
We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration.
Takeda
Yasuyuki
Y
Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, 16-13 Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan.
Yoshino
Toshiharu
T
Uoto
Kouichi
K
Chiba
Jun
J
Ishiyama
Takashi
T
Iwahana
Michio
M
Jimbo
Takeshi
T
Tanaka
Noriko
N
Terasawa
Hirofumi
H
Soga
Tsunehiko
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D017239:Paclitaxel