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)

• Published in: Journal of medicinal chemistry Vol. 46; no. 17; pp. 3766 - 3769
• Main Authors: Atigadda, Venkatram R, Vines, Kimberly K, Grubbs, Clinton J, Hill, Donald L, Beenken, Samuel L, Bland, Kirby I, Brouillette, Wayne J, Muccio, Donald D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14-08-2003
• Subjects: Animals; Anticarcinogenic Agents - chemical synthesis; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Drug Screening Assays, Antitumor; Fatty Acids, Unsaturated - chemical synthesis; Fatty Acids, Unsaturated - chemistry; Fatty Acids, Unsaturated - pharmacology; Female; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Naphthalenes - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid - agonists; Retinoid X Receptors; Stereoisomerism; Transcription Factors - agonists; Tretinoin - analogs & derivatives; Tretinoin - chemical synthesis; Tretinoin - pharmacology; Tumors; Stereoisomer; Rat; Rodentia; Retinoid; Malignant tumor; Anticarcinogen; Naphthalene derivatives; Biological activity; Prevention; Vertebrata; Mammalia; Carboxylic acid; Animal; Bicyclic compound; Aromatic compound; Mammary gland; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm030095q

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.