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

Abstract

The synthesis and antiulcer activity of highly strained cage compounds such as pentacyclo[4.2.0.02,5.03,8.04,7]-octane (cubane), pentacyclo[4.3.0.02,5.03,8.04,7]nonane (homocubane) and pentacyclo[5.3.0.02,4.03,6.05,8]decane are described. Of the compounds obtained, N[3-(3-piperidinomethylphenoxy)propyl]-4-piperidinocarbonylpenta-cyclo[4.2.0.02’5.03,8.04,7]octane carboxamide (26a) and N-[3’-(3’-piperidinomethylphenoxy)propyl]-l-bromo-9,9-ethylenedioxypentacyclo[4.3.0.02’5.03,8.04,7]nonane]-4-carboxamide (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. © 1993, The Pharmaceutical Society of Japan. All rights reserved.