A novel histamine 2(H2) receptor antagonist with gastroprotective activity. I. Synthesis and pharmacological evaluation of N- phenoxypropylacetamide derivatives with thioether function

Article abstract of DOI:10.1248/cpb.46.610

In an attempt to develop new types of anti-ulcer agents, a series of N- (phenoxypropyl)acetamide derivatives with a thioether moiety and their sulfur-oxidized analogues were synthesized and evaluated for histamine H₂- receptor antagonistic activity, Ca antagonistic activity and gastric anti- secretory activity in the lumen-perfuseed rat. Selected compounds were also tested for gastroprotective activity, which was expected to be based on Ca antagonistic activity. Structure-activity relationships are discussed. As a thioether moiety, -CH₂-S(O)p-CH₂-Ar (Ar; phenyl or furyl) was found to be optimal for the above activities. Especially, N-[3-[(3-(piperidinomethyl) phenoxy]propyl]acetamide with a benzyl sulfinyl, benzylsulfonyl, furfurylsulfinyl or furfuryisulfonyl group showed potent gastroprotective activity upon oral administration in a rat model. These compounds are candidates for novel anti-ulcer drugs with gastric anti-secretory and gastroprotective activities. 2-Furfurylsulfinyl-N-[3- [(piperidinomethyl)phenoxy]propyl]-acetamide was the most potent among the compounds tested and was given the code designation FRG-8701.

Full text of DOI:10.1248/cpb.46.610

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