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

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.