A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings

We recently found that N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide derivatives with a thioether function showed gastric anti-secretory and gastroprotective activities and that the thioether function (particularly furfurylthio or furfurylsulfinyl) was essential for gastroprotection. In the present study, a series of 2-furfurylthio and 2-furfurylsulfinyl acetamide derivatives were synthesized and evaluated for histamine H2 receptor antagonistic activity, gastric anti-secretory activity and gastroprotective action. Based on the structure of N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide, we designed compounds, in which the 3-(piperidinomethyl)phenoxy part is substituted with many types of heteroaromatic ring attached to the tertiary amine and the propyl group is replaced with other carbon linkages. Structure-activity relationships are discussed. 2-Furfurylsulfinyl-N-[4-[4-(piperidinomethyl)-2-pyridylox y]- (Z)-2-butenyl]acetamide was the most potent among the tested compounds and was given the code designation FRG-8813.