Antiulcer Agents. III. Synthesis and Antiulcer Activity of N-(3-(3-Piperidinomethylphenoxy)propyl)pentacyclo(4.2.0.02,5.03,8.04,7)octane Carboxamides and Related Compounds
| Autor: | Takeshi Hasegawa, Takao Kakita, Harumasa Toya, Hiromu Toyoda, Ikuo Ueda, Tomohiro Nigo |
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| Rok vydání: | 1993 |
| Předmět: |
Bridged-Ring Compounds
Male Magnetic Resonance Spectroscopy Ethanol medicine.drug_class Stereochemistry Acetal Antagonist Carboxamide General Chemistry General Medicine Anti-Ulcer Agents Rats Gastric Acid Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound chemistry In vivo Cubane Drug Discovery medicine Animals Nonane Octane |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 41:1760-1768 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.41.1760 |
| Popis: | The synthesis and antiulcer activity of highly strained cage compounds such as pentacyclo[4.2.0.0(2,5).0(3,8).0(4,7)]-octane (cubane), pentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)]nonane (homocubane) and pentacyclo[5.3.0.0(2,4).0(3,6).0(5,8)]decane are described. Of the compounds obtained, N-[3-(3-piperidinomethylphenoxy)propyl]-4-piperidinocarbonylpen tacyclo [4.2.0.0(2,5).0(3,8).0(4,7)]octane carboxamide (26a) and N-[3'-(3'-piperidinomethylphenoxy)propyl]-1-bromo-9, 9-ethylenedioxypentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)[nonane]-4- carboxamid e (26q) showed more potent antiulcer activity with very good cytoprotective ability in the HCl.ethanol-treated rat model. Compounds 26a and 26q exhibited H2-receptor antagonist potency (in vitro) comparable to that of ranitidine, but did not inhibit histamine-stimulated acid secretion (in vivo) in the gastric fistula rat model, when orally administered in the dose range at which antiulcer and cytoprotective activities were seen. The structure-activity relationships are discussed. |
| Databáze: | OpenAIRE |
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