Motilides, macrolides with gastrointestinal motor stimulating activity. II. Quaternary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal and 9,9-dihydroerythromycin A 6,9-epoxide.
Motilides, macrolides with gastrointestinal motor stimulating activity. II. Quaternary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal and 9,9-dihydroerythromycin A 6,9-epoxide.
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吗替利特、大环内酯类具有胃肠道运动刺激活性。
DOI：
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发表时间：
1989
影响因子：
1.7
通讯作者：
Z. Itoh
中科院分区：
文献类型：
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作者：
T. Sunazuka;K. Tsuzuki;S. Marui;H. Toyoda;S. Ōmura;N. Inatomi;Z. Itoh
制备了一系列8，9-脱水红霉素A6，9-半缩醛（1）和9，9-二氢红霉素A6，9-环氧化物（2）的季铵衍生物，并在狗体内进行了抗微生物活性和胃肠运动刺激（GMS）活性试验。当在1的二甲氨基上加入小的烷基卤和不饱和烷基卤如烯丙基溴和炔丙基溴时，GMS活性显著增强。其中，N-炔丙基-8，9-脱水红霉素A6，9-半缩醛溴化物（3）的GMS活性比红霉素A强2890倍，完全没有抗菌活性。在体外和体内，3的效力与合成的胃动素相当。
A series of quaternary ammonium derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal (1) and 9,9-dihydroerythromycin A 6,9-epoxide (2) has been prepared and tested for antimicrobial activity and gastrointestinal motor stimulating (GMS) activity in the dog (in vivo). The GMS activity is enhanced markedly when small alkyl halides and unsaturated alkyl halides such as allyl bromide and propargyl bromide are added to the dimethylamino group of 1. Among them, N-propargyl-8,9-anhydroerythromycin A 6,9-hemiacetal bromide (3) exhibits GMS activity 2890 times stronger than that of erythromycin A and is completely devoid of antimicrobial activity. The potency of 3 is comparable to that of synthetic motilin both in vitro and in vivo.