Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine

J Med Chem. 1976 Jan;19(1):6-10. doi: 10.1021/jm00223a002.


Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.

MeSH terms

  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Animals
  • Aziridines / chemical synthesis*
  • Aziridines / pharmacology
  • Azirines / chemical synthesis*
  • Cyclization
  • Dibenzylchlorethamine / analogs & derivatives*
  • Dibenzylchlorethamine / chemical synthesis
  • Dibenzylchlorethamine / pharmacology
  • Hydrolysis
  • Kinetics
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Phenoxybenzamine / analogs & derivatives*
  • Phenoxybenzamine / chemical synthesis
  • Phenoxybenzamine / pharmacology
  • Rats
  • Vas Deferens / drug effects


  • Adrenergic alpha-Antagonists
  • Aziridines
  • Azirines
  • Phenoxybenzamine
  • Dibenzylchlorethamine