New highly active taxoids from 9beta-dihydrobaccatin-9,10-acetals. Part 2.
To investigate structure-activity relationships of the 9,10-acetal-9beta-dihydro taxoids, we modified the 7-hydroxyl groups of the 9,10-acetonide-3'-(4-pyridyl) analogue to deoxy, methoxy, alpha-F, and 7beta,8beta-methano group. As a result of this study, we found that the 7-deoxy analogue was the strongest among these analogues. In addition, we found that the 7-deoxy-3'-(4-pyridyl) and 7-deoxy-3'-(2-pyridyl) analogues showed stronger activity against cell lines expressing P-glycoprotein than the corresponding 3'-phenyl analogue.
Ishiyama
Takashi
T
Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, 16-13 Kita-kasai 1-Chome Edogawa-ku, Tokyo, Japan.
Iimura
Shin
S
Yoshino
Toshiharu
T
Chiba
Jun
J
Uoto
Kouichi
K
Terasawa
Hirofumi
H
Soga
Tsunehiko
T
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D007202:Indicators and Reagents; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel