Bronchodilator and antiulcer phenoxypyrimidinones

J Med Chem. 1980 Sep;23(9):1026-31. doi: 10.1021/jm00183a012.

Abstract

Series of 5-phenoxy-2(1H)-pyrimidinones, 5-phenoxy-4(3H)-pyrimidinones, and related compounds were prepared in a follow-up of a lead prepared as a potential cyclic nucleotide regulating agent. Compounds were evaluated for bronchodilator activity in histamine-challenged guinea pigs and for anticulcer activity in a cold-restraint, stressed rat ulcer model. Bronchodilator activity comparable to, or greater than, that of theophylline was found in both the 2(1H)- and 4(3H)-pyrimidinone series and was most prominent in analogues containing either an electron-withdrawing or -donating substituent in the para position of the phenoxy ring. Significant antiulcer activity was observed only in the 2(1H)-pyrimidinone series among three closely related analogues. One of these, 5-(m-methylphenoxy)-2(1H)-pyrimidinone (3), exhibited more potent antiulcer effects than the clinically useful antiulcer agent carbenoxolone, without demonstrating bronchodilator activity.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis*
  • Bronchodilator Agents / chemical synthesis*
  • Female
  • Gastric Mucosa / drug effects
  • Guinea Pigs
  • Mucus / metabolism
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Anti-Ulcer Agents
  • Bronchodilator Agents
  • Pyrimidinones