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: Y F Shealy, C A Hosmer, J M Riordan, J W Wille, T S Rogers, D L Hill
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 37 Issue 19 Pg. 3051-6 (Sep 16 1994) ISSN: 0022-2623 [Print] United States
• PMID: 7932527 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anticarcinogenic Agents
• 4-oxoretinoic acid
• Tretinoin
• Ornithine Decarboxylase
• Tetradecanoylphorbol Acetate

Topics

• Alkylation
• Animals
• Anticarcinogenic Agents (chemical synthesis, therapeutic use)
• Cricetinae
• Drug Stability
• Enzyme Induction (drug effects)
• Female
• Magnetic Resonance Spectroscopy
• Mice
• Mice, Inbred Strains
• Ornithine Decarboxylase (biosynthesis)
• Papilloma (prevention & control)
• Skin (drug effects, enzymology)
• Skin Neoplasms (prevention & control)
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (pharmacology)
• Tretinoin (analogs & derivatives, chemical synthesis, therapeutic use)