title: 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.
abstract: 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.
authors.affiliation: Pharmaceuticals Research Laboratories, Fujirebio Inc., Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hirakawa
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Hosoda
authors.forename: A
authors.initials: A
authors.lastname: Sekine
authors.forename: T
authors.initials: T
authors.lastname: Yamaura
authors.forename: Y
authors.initials: Y
authors.lastname: Sekine
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D006632:Histamine