Cancer chemopreventive 3-substituted-4-oxoretinoic acids.
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.
Shealy
Y F
YF
Southern Research Institute, Birmingham, Alabama 35255-5305.
Hosmer
C A
CA
Riordan
J M
JM
Wille
J W
JW
Rogers
T S
TS
Hill
D L
DL
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
D016588:Anticarcinogenic Agents; C002202:4-oxoretinoic acid; D014212:Tretinoin; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate