[Synthesis and stereochemistry of potentially powerful analgesics: 2,4-m-diaryl substituted 3,7-diazabicyclo(3,3,1)nonan-9-one-1,5-diesters]

Arch Pharm (Weinheim). 1992 Oct;325(10):657-63. doi: 10.1002/ardp.19923251008.
[Article in German]

Abstract

The 2,4-di-2-pyridyl- substituted 7-methyl-3,7-diazabicyclo[3.3.1] nonan-9-one-1,5-diester shows a reasonable kappa-agonistic activity in the mouse vas deferens test. -To enhance the analgetic activity derivatives with m-Cl-, m-CH3-, m-OCH3-, m-OH-, and m-NO2 substituted phenyl residues at C-2/4 were synthesized: From the condensation of benzaldehydes, methylamine, and oxoglutarate isomeric mixtures of piperidones were obtained, containing cis-ketone and -enol and trans-enol; the isomerisation reactions of these piperidones were observed in CDCl3 and CD3OD. The bicyclus resulting from the reaction of the piperidones with HCHO and methylamine exhibits conformational rigidity because the free rotation of the 2,4-aryl groups is hindered. The rotational barrier around the C-2-aryl-bond was shown to be 18 kcal/mol by analysis of variable temp. 1H-NMR spectra.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / pharmacology
  • Animals
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / pharmacology
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Narcotics / chemical synthesis*
  • Narcotics / pharmacology
  • Receptors, Opioid, kappa / drug effects
  • Vas Deferens / drug effects

Substances

  • Analgesics
  • Aza Compounds
  • Bridged Bicyclo Compounds
  • Narcotics
  • Receptors, Opioid, kappa