Structure of grepafloxacin relative to activity and safety profile.
Structure of grepafloxacin relative to activity and safety profile.
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DOI：
10.1111/j.1469-0691.1998.tb00684.x
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发表时间：
1998-03-01
期刊：
影响因子：
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通讯作者：
Hooper, David C.
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文献类型：
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作者：
Hooper, David C.
环丙沙星和格帕沙星的结构比较表明，这两种化合物是相似的，但有两个例外：格帕沙星在5位有一个甲基，在7-哌嗪基取代基上有一个甲基。在1位，两种化合物都有一个环丙基，这对效力很重要，但限制了厌氧活性。格帕沙星中7位的甲基哌嗪与其增强的革兰氏阳性活性和长半衰期相关。在R5处的甲基也被认为增强革兰氏阳性活性。环丙沙星在7位的哌嗪基团与良好的革兰氏阴性活性相关。对流感嗜血杆菌、卡他莫拉菌和肠道革兰氏阴性杆菌，格帕沙星的革兰氏阴性活性与环丙沙星相当。对氟喹诺酮类药物的耐药性研究表明，格帕沙星与金黄色葡萄球菌耐药性选择性降低相关，这可能与诺拉抑制或避免外排转运有关。
A comparison of the structure of ciprofloxacin and grepafloxacin shows that the two compounds are similar, with two exceptions: grepafloxacin has a methyl group at the 5 position and a methyl group attached to the 7-piperazinyl substituent. At the 1 position, both compounds have a cyclopropyl group, which is important for potency, but limits anaerobic activity. The methylpiperazine at position 7 in grepafloxacin is associated with its enhanced Gram-positive activity and long half-life. The methyl group at R5 is also thought to enhance Gram-positive activity. Ciprofloxacin's piperazine group at the 7 position is associated with good Gram-negative activity. Grepafloxacin's Gram-negative activity is comparable to that of ciprofloxacin's against Haemophilus influenzae, Moraxella catarrhalis and enteric Gram-negative bacilli. Studies of resistance development to fluoroquinolones suggest that grepafloxacin is associated with a reduced selection of resistance in Staphylococcus aureus, which is possibly related to the inhibition or avoidance of efflux transport by NorA.