5,6,7,8-Tetrahydroguinolines. 4. Antiulcer and antisecretory activity of 5,6,7,8-tetrahydroquinolinenitriles and -thioamides.
A number of 5,6,7,8-tetrahydroquinoling-8-nitriles and -8-thioamides and related compounds have been found to be potent inhibitors of basal gastric secretion in the pylorus-ligated rat and to afford protection against gastric erosions induced in rats by cold-restraint stress. Molecular manipulation has proved useful in determining factors necessary for such activity and structure-activity relationships are discussed. It has been shown that the most necessary requirements for activity are a pyridine nitrogen with its available lone pair and a primary or secondary thioamide. Also desirable is a six-membered carbocyclic ring with relative freedom from steric hinderance around the 8 position.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D008026:Ligation; D008297:Male; D009570:Nitriles / Q000138:chemical synthesis / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013276:Stomach Ulcer / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D009570:Nitriles; D011804:Quinolines; D013854:Thioamides