Bronchodilator and antiulcer phenoxypyrimidinones.
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.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D001993:Bronchodilator Agents / Q000138:chemical synthesis*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D009093:Mucus / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D001993:Bronchodilator Agents; D011744:Pyrimidinones