A Novel Histamine 2(H2) Receptor Antagonist with Gastroprotective Activity. I. Synthesis and Pharmacological Evaluation of N-Phenoxypropylacetamide Derivatives with Thioether Function
| Autor: | Tetsuaki Yamaura, Noriaki Kashiwaba, Yasuo Sekine, Matsumoto Hajime, Teruo Kutsuma, Hirakawa Nobuhiko, Akihiro Sekine |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.drug_class Stereochemistry Administration Oral Carboxamide Sulfides Chemical synthesis Gastric Acid Structure-Activity Relationship chemistry.chemical_compound Piperidines Thioether Histamine H2 receptor Acetamides Drug Discovery medicine Animals Moiety Structure–activity relationship Benzothiazoles Rats Wistar Chemistry Stomach General Chemistry General Medicine Anti-Ulcer Agents Calcium Channel Blockers Rats Perfusion Thiazoles Histamine H2 Antagonists Histamine Acetamide |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 46:610-615 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.46.610 |
| Popis: | 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 furfurylsulfonyl 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]ac etamide was the most potent among the compounds tested and was given the code designation FRG-8701. |
| Databáze: | OpenAIRE |
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