Synthesis and anticonvulsant activity of some 2/3-benzoylaminopropionanilide derivatives

Arzneimittelforschung. 2012 Jun;62(6):295-300. doi: 10.1055/s-0032-1308982. Epub 2012 Apr 2.

Abstract

In this study, the synthesis and anticonvulsant properties of sixteen 2/3-benzoylaminopropionanilide derivatives were described. Molecular design of the compounds has been based on the modification of lacosamide which is a functionalized amino acid with a novel anticonvulsant activity. The structural confirmation of the title compounds was achieved by spectral and analytical data. The anticonvulsant activity profile of synthesized compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) seizure tests, whereas their neurotoxicity was examined using rotarod test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. The majority of the compounds were effective in the MES or scMet screening tests. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. Most active compounds in the series were 3, 12 and 13, which bearing 2-methyl, 2-ethyl and 2-isopropyl substituent on the N-phenyl ring, respectively.

MeSH terms

  • Acetamides / chemistry
  • Anilides / chemical synthesis*
  • Anilides / chemistry
  • Anilides / pharmacology*
  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacology*
  • Benzoates / chemical synthesis*
  • Benzoates / pharmacology*
  • Convulsants
  • Electroshock
  • Injections, Subcutaneous
  • Lacosamide
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Neurotoxicity Syndromes / psychology
  • Pentylenetetrazole
  • Postural Balance / drug effects
  • Seizures / chemically induced
  • Seizures / prevention & control
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Anilides
  • Anticonvulsants
  • Benzoates
  • Convulsants
  • Lacosamide
  • Pentylenetetrazole