Studies on antiulcer agents. II. Antiulcer properties of N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides inhibiting release of histamine from passively sensitized rat peritoneal mast cells.
With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.
Terashima
K
K
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Tanimura
T
T
Shimamura
H
H
Kawase
A
A
Uenishi
K
K
Tanaka
Y
Y
Kimura
I
I
Kamisaki
T
T
Ishizuka
Y
Y
Sato
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin; D002927:Cimetidine / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D000431:Ethanol; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D006634:Histamine H1 Antagonists; D011743:Pyrimidines; D013777:Tetrazoles; D062367:ortho-Aminobenzoates; D000431:Ethanol; D002927:Cimetidine; C012293:tranilast; D004205:Cromolyn Sodium; D001241:Aspirin