Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity

J Med Chem. 1992 Jun 26;35(13):2446-51. doi: 10.1021/jm00091a012.


As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis*
  • Anti-Ulcer Agents / pharmacology
  • Gastric Acidity Determination
  • Gastric Mucosa / drug effects
  • Guinea Pigs
  • Histamine H2 Antagonists / chemical synthesis*
  • Histamine H2 Antagonists / pharmacology
  • In Vitro Techniques
  • Male
  • Phenylurea Compounds / chemical synthesis
  • Phenylurea Compounds / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis*
  • Urea / pharmacology


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Phenylurea Compounds
  • Urea