Synthesis of 6-thiosubstituted 5-ethoxycarbonyl-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones, 6-substituted 5-hydroxy-1,3-diphenyl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their esters with local anesthetic, antiarrhythmic, antiinflammatory and analgesic activities

Farmaco. 1997 Aug-Sep;52(8-9):547-55.

Abstract

The synthesis of 6-thiosubstituted 5-ethoxycarbonyl-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin- 4(1H)-ones 3, and of 6-substituted 5-hydroxy-1,3-diphenyl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones 5 and their esters 6 is described. These derivatives were prepared in order to evaluate the influence on the pharmacological profile of alkyl substituents bearing polar/hydrophilic functionalities at an enethiol substructure as in compounds 3 or to assess the effects arising from the incorporation of the sulfur atom in a thiophene moiety as in thienopyrimidinones 5 and 6 in comparison with a series of 5-substituted 6-acylthio-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 1c,d, previously described. Preliminary screenings suggest that all tested compounds maintained or even increased the local anesthetic activity, but failed in the platelet antiaggregating activity; on the other hand, antiarrhythmic and antiinflammatory activity was preserved in some esters 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / chemical synthesis*
  • Anesthetics, Local / pharmacology
  • Animals
  • Anti-Arrhythmia Agents / chemical synthesis*
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Edema / chemically induced
  • Edema / drug therapy
  • In Vitro Techniques
  • Mice
  • Pain Measurement / drug effects
  • Platelet Aggregation / drug effects
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology
  • Rats

Substances

  • Anesthetics, Local
  • Anti-Arrhythmia Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrimidinones