Antiulcer agents. III. Synthesis and antiulcer activity of N-[3-(3-piperidinomethylphenoxy)propyl]pentacyclo[4.2.0.0(2,5).0(3,8).0 (4,7)]-octane carboxamides and related compounds.
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.
Hasegawa
T
T
Institute of Scientific and Industrial Research, Osaka University, Japan.
Nigo
T
T
Kakita
T
T
Toyoda
H
H
Toya
H
H
Ueda
I
I
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D001952:Bridged-Ring Compounds; C085275:N-(3-(3-piperidinomethylphenoxy)propyl)-4-piperidinocarbonylpentacyclo(4.2.0.0(2,5).0(3,8).0(4,7))octane carboxamide; C085276:N-(3'-(3'-piperidinomethylphenoxy)propyl)-1-bromo-9,9-ethylenedioxypentacyclo(4.3.0.0(2,5).0(3,8).0(4,7)nonane)-4-carboxamide