Synthesis and Pharmacological Characterization of New H2‐Antagonists Containing NO‐Donor Moieties,Endowed with Mixed Antisecretory and Gastroprotective Activities

Synthesis, structural characterization, and pharmacological profile of a series of H₂‐antagonists able to release nitric oxide (NO) are reported. These compounds were obtained by using appropriate spacers to join H₂‐antagonistic pharmacophoric groups related to lamtidine and tiotidine to different NO‐donor moieties such as esters of HNO₃, nitrosothio groups, and benzenesulfonyl‐substituted furoxans. All of the compounds were tested for their NO‐donor properties. Furthermore, the hybrid structures synthesized, together with some selected reference compounds, were tested for their H₂‐antagonistic properties, both in vitro and in vivo, and for their gastroprotective effects. Only the hybrid compounds were able both to antagonize histamine effects on guinea‐pig papillary muscle and to display in vivo antisecretory and gastroprotective action. The best results were obtained with the lamtidine/furoxan hybrid structure.