Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams

J Med Chem. 1993 May 28;36(11):1511-9. doi: 10.1021/jm00063a001.

Abstract

A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3-(trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system.

MeSH terms

  • Amnesia / drug therapy*
  • Amnesia / etiology
  • Animals
  • Brain / enzymology
  • Cholinesterase Inhibitors / pharmacology
  • Drug Design
  • Electroshock
  • In Vitro Techniques
  • Lactams / chemical synthesis*
  • Lactams / pharmacology
  • Male
  • Mice
  • Psychotropic Drugs / chemical synthesis*
  • Psychotropic Drugs / pharmacology
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Inbred F344
  • Scopolamine
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Lactams
  • Psychotropic Drugs
  • Pyrrolidinones
  • Scopolamine