26-tert-butyl-N-[2-(difluoromethyl)-1-[(1-methylcyclopropyl)sulfonylcarbamoyl]cyclopropyl]-13,13-difluoro-24,27-dioxo-2,17,23-trioxa-4,11,25,28-tetrazapentacyclo[26.2.1.03,12.05,10.018,22]hentriaconta-3,5,7,9,11,14-hexaene-29-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 26-tert-butyl-N-[2-(difluoromethyl)-1-[(1-methylcyclopropyl)sulfonylcarbamoyl]cyclopropyl]-13,13-difluoro-24,27-dioxo-2,17,23-trioxa-4,11,25,28-tetrazapentacyclo[26.2.1.03,12.05,10.018,22]hentriaconta-3,5,7,9,11,14-hexaene-29-carboxamide
• 化学式: C₃₈H₄₆F₄N₆O₉S
• 分子量: 838.9
• InChiKey: MLSQGNCUYAMAHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  58
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  204
• 氢给体数：
  3
• 氢受体数：
  15

ADMET

毒理性

• 肝毒性

在大规模随机对照试验中，Mavyret治疗期间血清转氨酶水平迅速下降，且仅有少数情况下出现晚期、新发的丙氨酸氨基转移酶（ALT）或天门冬氨酸氨基转移酶（AST）升高，这些升高通常是轻到中度的，并且在接受治疗的患者中，升高超过上限正常值（ULN）5倍的情况不到1%。此外，Mavyret治疗期间没有与肝功能失代偿的病例相关，也没有与慢性乙型肝炎的再激活相关，这两种严重并发症已与其他口服治疗慢性丙型肝炎的方案相关。然而，Mavyret尚未获批用于有晚期肝硬化（Child B级或C级）的患者，其在普通实践中的使用也受到限制。尽管如此，Mavyret的产品标签上有一个黑框警告，提示可能会引起乙型肝炎的再激活，并且建议在开始治疗前筛查乙肝表面抗原（HBsAg）和乙肝核心抗体（anti-HBc），如果这些标志物存在，则需要谨慎监测。

In large randomized controlled trials, serum aminotransferase levels decreased rapidly during Mavyret therapy and there were only rare instances of late, de novo elevations in ALT or AST that were usually mild-to-moderate in degree and rising to more than 5 times ULN in less than 1% of treated subjects. In addition, Mavyret has not been linked to instances of hepatic decompensation during treatment of patients with preexisting cirrhosis nor with reactivation of chronic hepatitis B, two serious complications that have been linked to other oral regimens to treat chronic hepatitis C. However, Mavyret has not been approved for use in patients with advanced cirrhosis (Child Class B or C) and its overall use in general practice has been limited. Nevertheless, the product label for Mavyret has a boxed warning for reactivation of hepatitis B and screening for HBsAg and anti-HBc is recommended before starting therapy, with careful monitoring if these markers are present.

来源:LiverTox