Antitumor activity of 9(R)-dihydrotaxane analogs.
A novel reduced taxane, 13-acetyl-9(R)-dihydrobaccatin III (1) has been isolated from Taxus canadensis. The selective C-13 deacetylation of this isolate has allowed for the preparation of a wide variety of 9(R)-dihydrotaxane analogs. In general, this series has shown greater stability and water solubility than the 9-carbonyl series while retaining antimicrotubule and tumor cell cytotoxicity activities relative to taxol. Placement of polar functionalities at the C-7 position results in loss of activity whereas alkylation or acylation of either C-7 or C-9 hydroxyl groups ameliorate the activity.
Klein
L L
LL
Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
Li
L
L
Maring
C J
CJ
Yeung
C M
CM
Thomas
S A
SA
Grampovnik
D J
DJ
Plattner
J J
JJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel