Synthesis and Stereochemistry of Potential Opioid-Like 2,4-M-Diarylsubstituted 3,7-Diazabicyclo[3.3.1]Nonan-9-One-1,5-Diesters

WOS: A1992JX81300007PubMed ID: 1334646The 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. H-1-NMR spectra