Conformationally defined retinoic acid analogues. 5. Large-scale synthesis and mammary cancer chemopreventive activity for (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30).

Abstract

Retinoids that activate the nuclear retinoid X receptors (RXRs) display potential for chemoprevention of breast cancer. We previously reported that 9cUAB30 (1) is an RXR-selective retinoid. To explore its in vivo chemopreventive activity, multigram quantities of 1 were needed. Here, we describe a modified synthesis that yields up to 100 g of 1. We further demonstrate that 1 is very effective in the prevention of N-methyl-N-nitrosourea induced mammary cancers in rats without signs of toxicity.

• Authors: Venkatram R Atigadda, Kimberly K Vines, Clinton J Grubbs, Donald L Hill, Samuel L Beenken, Kirby I Bland, Wayne J Brouillette, Donald D Muccio
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 17 Pg. 3766-9 (Aug 14 2003) ISSN: 0022-2623 [Print] United States
• PMID: 12904083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Fatty Acids, Unsaturated
• Naphthalenes
• Receptors, Retinoic Acid
• Retinoid X Receptors
• Transcription Factors
• Tretinoin
• UAB 30

Topics

• Animals
• Anticarcinogenic Agents (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Fatty Acids, Unsaturated (chemical synthesis, chemistry, pharmacology)
• Female
• Mammary Neoplasms, Experimental (prevention & control)
• Naphthalenes (chemical synthesis, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Retinoic Acid (agonists)
• Retinoid X Receptors
• Stereoisomerism
• Transcription Factors (agonists)
• Tretinoin (analogs & derivatives, chemical synthesis, pharmacology)