Muto Y, Ichikawa H, Seiki M, Shirataki Y, Yokoe I, Komatsu M
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Yakugaku Zasshi. 1995 Apr;115(4):318-28. doi: 10.1248/yakushi1947.115.4_318.
It was found that (+/-)ethyl 2-[2-(3-hydroxypropyl)-4-oxocyclohexylidene-propionate (1), (+/-)ethyl 2-[2-(3-hydroxypropyl)-4,5-dimethoxyphenyl]propionate (2), (+/-)3-[2-(3-hydroxypropyl)-4,5-dimethoxyphenyl]-2-butanone (3) and (+/-)2-[2-(3-hydroxypropyl)-4-methoxy-5-(2- piperidinoethoxy)phenyl]cyclopentanone (4) had potent antiulcer activities. In order to study structure-activity relationships, (+/-)3-[(3-hydroxypropyl)phenoxy]-2-butanone derivatives (5, 6) were synthesized and tested for antiulcer activities. Among them, (+/-)3-[2-(3-hydroxypropyl)-4-methoxy-5-[3-(4- methylpiperidino)propoxy]phenoxy]-2-butanone.3/2 oxalate (6k) was selected as a preferred antiulcer agent.
研究发现，（±）-2-[2-(3-羟丙基)-4-氧代环己叉基]丙酸乙酯（1）、（±）-2-[2-(3-羟丙基)-4,5-二甲氧基苯基]丙酸乙酯（2）、（±）-3-[2-(3-羟丙基)-4,5-二甲氧基苯基]-2-丁酮（3）和（±）-2-[2-(3-羟丙基)-4-甲氧基-5-(2-哌啶基乙氧基)苯基]环戊酮（4）具有强效抗溃疡活性。为研究构效关系，合成了（±）-3-[(3-羟丙基)苯氧基]-2-丁酮衍生物（5、6）并测试其抗溃疡活性。其中，（±）-3-[2-(3-羟丙基)-4-甲氧基-5-[3-(4-甲基哌啶基)丙氧基]苯氧基]-2-丁酮·3/2草酸盐（6k）被选为优选的抗溃疡药物。
