title: Cancer chemopreventive 3-substituted-4-oxoretinoic acids.
abstract: The introduction of substituents at position 3 of methyl 4-oxoretinoate can be effected in good yields by alkylating the lithium dienolate. A second substituent can be introduced also, but the resulting 3,3-disubstituted-4-oxoretinoates were isolated in lower yields. Evidence was obtained for a slower rate of alkylation at the alpha-position (carbon 14) of the ester group. Some of these 4-oxoretinoic acid analogues showed high activity in assays in vivo for the inhibition of ornithine decarboxylase activity and carcinogen-induced papillomas in mouse skin.
authors.affiliation: Southern Research Institute, Birmingham, Alabama 35255-5305.
authors.forename: Y F
authors.initials: YF
authors.lastname: Shealy
authors.forename: C A
authors.initials: CA
authors.lastname: Hosmer
authors.forename: J M
authors.initials: JM
authors.lastname: Riordan
authors.forename: J W
authors.initials: JW
authors.lastname: Wille
authors.forename: T S
authors.initials: TS
authors.lastname: Rogers
authors.forename: D L
authors.initials: DL
authors.lastname: Hill
mesh_terms: D000478:Alkylation; D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use*; D006224:Cricetinae; D004355:Drug Stability; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010212:Papilloma / Q000517:prevention & control; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D012878:Skin Neoplasms / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; C002202:4-oxoretinoic acid; D014212:Tretinoin; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate