Phosphonate Derivatives of Paracetamol and Valproic Acid

ChemMedChem. 2023 Feb 14;18(4):e202200526. doi: 10.1002/cmdc.202200526. Epub 2022 Nov 24.

Abstract

Paracetamol and valproic acid are standalone drugs with leading position in the world drug market. The phosphonate analogues of these drugs were synthesized and were tested in vivo. N-(4-hydroxyphenylcarbamoyl)phosphonic acid was four times more potent than paracetamol in preventing acetic acid-induced writhing. Phosphonate derivative of valproic acid, (2-propylpentanoyl)phosphonic acid, had similar in vivo activity to valproic acid in the pentylenetetrazole-induced kindling mouse model.

Keywords: bioisosteres; drug analogues; paracetamol; phosphonates; valproic acid.

MeSH terms

  • Acetaminophen / pharmacology
  • Animals
  • Mice
  • Organophosphonates* / pharmacology
  • Phosphorous Acids / pharmacology
  • Valproic Acid* / pharmacology

Substances

  • Valproic Acid
  • phosphonic acid
  • Acetaminophen
  • Organophosphonates
  • Phosphorous Acids