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).
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.
Atigadda
Venkatram R
VR
Department of Chemistry, University of Alabama at Birmingham, 901 South 14th Street, Birmingham, AL 35294, USA.
Vines
Kimberly K
KK
Grubbs
Clinton J
CJ
Hill
Donald L
DL
Beenken
Samuel L
SL
Bland
Kirby I
KI
Brouillette
Wayne J
WJ
Muccio
Donald D
DD
D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors; D013237:Stereoisomerism; D014157:Transcription Factors / Q000819:agonists; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; C112106:UAB 30