Santilli A A, Scotese A C, Bauer R F, Bell S C
Research Division, Wyeth Laboratories, Inc., Radnor, Pennsylvania 19087.
J Med Chem. 1987 Dec;30(12):2270-7. doi: 10.1021/jm00395a015.
The syntheses of 2-oxo-1,8-naphthyridine-3-carboxylic acid derivatives having potent gastric antisecretory properties in the pyloric-ligated (Shay) rat model are described. Two of the more potent compounds tested that were selected for more detailed dose-response evaluation were 4-amino-1-ethyl-1,2-dihydro-2-oxonaphthyridine-3-carboxylic acid ethyl ester (35) and 1-ethyl-1,2-dihydro-7-methyl-4-(4-methyl-1-piperazinyl)-2- oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester (77). These compounds lowered total acid output in the rat in a dose-related fashion. Both compounds were more potent than cimetidine when tested in the rat. Both 35 and 77 showed inhibitory activity in food-stimulated acid secretion in the Pavlov-pouch, conscious dog. The mechanism of action for this series is not known. Details of structure-activity relationships are described.
本文描述了在幽门结扎（ Shay ）大鼠模型中具有强效胃抗分泌特性的 2- 氧代 -1,8- 萘啶 -3- 羧酸衍生物的合成。经测试，被选作更详细剂量 - 反应评估的两种活性更强的化合物分别是 4- 氨基 -1- 乙基 -1,2- 二氢 -2- 氧代萘啶 -3- 羧酸乙酯（ 35 ）和 1- 乙基 -1,2- 二氢 -7- 甲基 -4-(4- 甲基 -1- 哌嗪基 )-2- 氧代 -1,8- 萘啶 -3- 羧酸乙酯（ 77 ）。这些化合物以剂量相关的方式降低了大鼠的总酸分泌量。在大鼠实验中，这两种化合物均比西咪替丁更有效。 35 和 77 在清醒的巴甫洛夫小胃犬的食物刺激胃酸分泌实验中均表现出抑制活性。该系列化合物的作用机制尚不清楚。文中描述了构效关系的细节。
