Synthesis and beta-adrenergic blocking activity of new aliphatic and alicyclic oxime ethers

J Med Chem. 1984 Oct;27(10):1291-4. doi: 10.1021/jm00376a011.

Abstract

We describe the synthesis and pharmacological properties of two new series of aliphatic and alicyclic beta-adrenergic blockers, most of them containing a cyclopropyl ring. They belong either to 2-hydroxy-3-(tert-butylamino)propyl ether A or 2-hydroxy-3-tert-(butylamino)propyl ketoxime ether B derivatives. The O-[2-hydroxy-3-(tert-butylamino)propyl] dicyclopropyl ketoxime 5 exhibited a beta-adrenergic antagonist activity comparable to that of propranolol. It was found that ketoxime ethers B generally showed higher potency than the corresponding ethers A. We confirm that the presence of an aromatic nucleus is not crucial for the beta-adrenergic activity. Structure-activity relationships among these series are discussed.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Antagonists / chemical synthesis*
  • Animals
  • Ethers / chemical synthesis*
  • Ethers / pharmacology
  • Guinea Pigs
  • Heart Rate / drug effects
  • Indicators and Reagents
  • Isoproterenol / pharmacology
  • Magnetic Resonance Spectroscopy
  • Muscle Relaxation / drug effects
  • Oximes / chemical synthesis*
  • Oximes / pharmacology
  • Receptors, Adrenergic, beta / drug effects
  • Structure-Activity Relationship
  • Trachea / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Ethers
  • Indicators and Reagents
  • Oximes
  • Receptors, Adrenergic, beta
  • Isoproterenol