Synthesis and cognition activating properties of some mono- and bicyclic lactam derivatives

J Med Chem. 1988 Nov;31(11):2153-8. doi: 10.1021/jm00119a016.

Abstract

Upon reductive cyclization cyano esters 2, 3, and 9 yielded piperidones and perhydropyrrolo[3,4-c]pyridine lactams, generally as a mixture of diasteromeric cis-trans forms. X-ray crystallographic analyses were carried out on bicyclic dilactam derivatives 6 and 10, and a cis configuration at the ring junction was determined in both cases. A series of neuropsychopharmacological tests performed on the title compounds indicated that they are generally nontoxic even at high doses (up to 1000 mg/kg ip). The cognition activating properties of lactams 4, 5, 6, and 10 were evaluated in enhancing retention for passive avoidance learning in rats without and after electroconvulsive shock (ECS); compounds 5 and 10 were found to be more potent than piracetam in the amnesia-reversal testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnesia / prevention & control
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged-Ring Compounds / chemical synthesis*
  • Cognition / drug effects*
  • Lactams / chemical synthesis*
  • Lactams / pharmacology
  • Rats
  • X-Ray Diffraction

Substances

  • Bridged Bicyclo Compounds
  • Bridged-Ring Compounds
  • Lactams