Structure-Activity study of retinoid agonists bearing substituted dicarba-closo-dodecaborane. Relation between retinoidal activity and conformation of two aromatic nuclei

Bioorg Med Chem Lett. 2001 May 21;11(10):1307-11. doi: 10.1016/s0960-894x(01)00204-9.

Abstract

We have investigated the structure activity relationships of the potent retinoid agonist, 4-[4-(2-propyl-1,2-dicarba-closo-dodecaboran-l-yl)phenylamino]benzoic acid (BR403), which we have previously reported. Substitution of a methyl group on the aromatic nucleus or a methyl group on the nitrogen atom, or replacement of the amino group with ether, methylene, carboxyl or 1,1-ethylene greatly decreased the activity. The relatively planar conformation at the phenyl-N-phenyl moiety seems to play a critical role in the appearance of the biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / chemistry
  • Benzoates / pharmacology
  • Boranes / chemical synthesis*
  • Boranes / chemistry
  • Boranes / pharmacology
  • Boron Neutron Capture Therapy
  • COS Cells
  • Cell Differentiation / drug effects
  • Dose-Response Relationship, Drug
  • HL-60 Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Receptors, Retinoic Acid / agonists
  • Retinoids / agonists*
  • Structure-Activity Relationship
  • Transcriptional Activation / drug effects

Substances

  • 4-(4-(2-propyl-1,2-dicarba-closo-dodecaboran-l-yl)phenylamino)benzoic acid
  • Benzoates
  • Boranes
  • Receptors, Retinoic Acid
  • Retinoids