Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.
As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.
Kyorin Pharmaceutical Company, Ltd., Technical Center of Organic Syntheses, Okaya-shi, Japan.
M
M
Miyashita
T
T
Matsumoto
H
H
Matsukubo
F
F
Iinuma
F
F
Taga
H
H
Sekiguchi
K
K
Hamada
K
K
Okamura
K
K
Nishino
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010671:Phenylurea Compounds; D014508:Urea