An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives

J Med Chem. 1985 Feb;28(2):153-60. doi: 10.1021/jm00380a001.

Abstract

On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenoceptors; the beta 2/beta 1 selectivity ratio indicated that they are more active on the tracheal than on the cardiac beta-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other beta-blocking drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / chemical synthesis*
  • Animals
  • Chemical Phenomena
  • Chemistry, Physical
  • Guinea Pigs
  • Heart Atria / drug effects
  • Isoproterenol / pharmacology
  • Male
  • Models, Molecular
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, beta / metabolism*
  • Structure-Activity Relationship
  • Trachea / drug effects
  • Vas Deferens / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Isoproterenol