Motilides, macrolides with gastrointestinal motor stimulating activity. I. O-substituted and tertiary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal.
Motilides, macrolides with gastrointestinal motor stimulating activity. I. O-substituted and tertiary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal.
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DOI：
10.1248/cpb.37.2687
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发表时间：
1989-10
影响因子：
1.7
通讯作者：
K. Tsuzuki;T. Sunazuka;S. Marui;Hajime Toyoda;S. Ōmura;N. Inatomi;Z. Itoh
中科院分区：
文献类型：
--
作者：
K. Tsuzuki;T. Sunazuka;S. Marui;Hajime Toyoda;S. Ōmura;N. Inatomi;Z. Itoh
8，9-脱水红霉素A 6，9-半缩醛（1）的胃肠运动刺激（GMS）活性比红霉素A（EM-A）强10倍，对其进行化学修饰，以寻找具有更强GMS活性且无抗菌活性的衍生物;详细信息见本文和后续论文。用乙基和异丙基取代1的二甲氨基的甲基，分别得到去（N-甲基）-N-乙基-8，9-脱水红霉素A 6，9-半缩醛（55）和去（N-甲基）-N-异丙基-8，9-脱水红霉素A 6，9-半缩醛（58）。它们表现出明显的GMS活性，没有抗菌活性。特别是，58的GMS活性提高到EM-A的248倍。EM-A及其衍生物可模拟犬的外源性胃动素。命名为“胃动素”，意思是胃动素样的大环内酯，建议为这个新家族的大环内酯化合物。
Chemical modifications of 8,9-anhydroerythromycin A 6,9-hemiacetal (1), which showed gastrointestinal motor stimulating (GMS) activity 10 times more potent than that of erythromycin A (EM-A), were undertaken to search for derivatives having stronger GMS activity and no antimicrobial activity; details are described in this and a subsequent paper. Displacement of a methyl group of the dimethylamino group of 1 with an ethyl group and an isopropyl group provided de(N-methyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal (55) and de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (58), respectively. They showed significant GMS activity and no antibacterial activity. In particular, the GMS activity of 58 was increased to 248 times that of EM-A. EM-A and the derivatives obtained in this study mimic exogenous motilin in the dog. The name "motilide", meaning a motilin-like macrolide, is proposed for this new family of macrolide compounds.