title: Synthesis and biological evaluation of C-3'-modified analogs of 9(R)-dihydrotaxol.
abstract: Taxol (1) is considered a most exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihydrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family. Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino group might be optimal. However, relatively little is known about the effects of the 3'-phenyl ring on activity. The synthesis and biological evaluation of analogs of 3 modified at the C-3' position are described. This study revealed that the 3'-phenyl ring was not required for activity and identified several compounds which had equal or greater in vitro and in vivo activity than taxol.
authors.affiliation: Anti-Infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: S A
authors.initials: SA
authors.lastname: Thomas
authors.forename: L L
authors.initials: LL
authors.lastname: Klein
authors.forename: C M
authors.initials: CM
authors.lastname: Yeung
authors.forename: C J
authors.initials: CJ
authors.lastname: Maring
authors.forename: D J
authors.initials: DJ
authors.lastname: Grampovnik
authors.forename: P A
authors.initials: PA
authors.lastname: Lartey
authors.forename: J J
authors.initials: JJ
authors.lastname: Plattner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D007202:Indicators and Reagents; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D043823:Taxoids; C088970:9-dihydrotaxol; D017239:Paclitaxel