4-(dimethylamino)-7-fluoro-1,10,11,12a-tetrahydroxy-3,12-dioxo-9-[(2-pyrrolidin-1-ylacetyl)amino]-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 4-(dimethylamino)-7-fluoro-1,10,11,12a-tetrahydroxy-3,12-dioxo-9-[(2-pyrrolidin-1-ylacetyl)amino]-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
• 化学式: C₂₇H₃₁FN₄O₈
• 分子量: 558.6
• InChiKey: AKLMFDDQCHURPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  194
• 氢给体数：
  6
• 氢受体数：
  11

ADMET

毒理性

• 肝毒性

在静脉注射埃拉卡青霉素的初步临床试验中，血清转氨酶升高的情况是轻微的，并不比安慰剂或比较治疗组的更频繁。没有因埃拉卡青霉素导致的临床上明显的肝损伤的实例。尽管如此，其他四环素类抗生素是众所周知的药物诱导肝损伤的原因。特别是，高剂量的静脉注射四环素已知能够引起严重的肝微小囊泡脂肪变性与乳酸酸中毒以及严重的肝功能障碍（LASH综合症）。因此，静脉注射四环素已从使用中撤回。这种并发症尚未在静脉注射埃拉卡青霉素、奥马卡青霉素或替加卡青霉素中出现。四环素类抗生素还与具有自身免疫特征的特异质性肝损伤有关，这通常在使用长期后出现，并且最常见与米诺卡青霉素有关。这种并发症也尚未在埃拉卡青霉素、奥马卡青霉素或替加卡青霉素中报告。

In preclinical trials of intravenous eravacycline, serum aminotransferase elevations were mild and no more frequent than with placebo or comparator treatment arms. There were no instances of clinically apparent liver injury that could be attributed to eravacycline. Nevertheless, other tetracycline antibiotics are well known causes of drug induced liver injury. In particular, high doses of intravenous tetracycline are known to be able to cause severe hepatic microvesicular steatosis with lactic acidosis and severe hepatic dysfunction (LASH syndrome). For this reason, intravenous tetracycline was withdrawn from use. This complication has not been reported with intravenous eravacycline, omadacycline or tigecycline. The tetracyclines have also been linked to idiosyncratic liver injury with autoimmune features that generally arise with long term use and has most commonly been associated with minocycline. This complication also has not been reported with eravacycline, omadacycline or tigecycline.

来源:LiverTox