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)

J Med Chem. 2003 Aug 14;46(17):3766-9. doi: 10.1021/jm030095q.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / chemical synthesis*
  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / pharmacology
  • Female
  • Mammary Neoplasms, Experimental / prevention & control*
  • 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

Substances

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