格来普韦 | 1365970-03-1

• 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
• 中文名称: 格来普韦
• 中文别名: 格拉卡匹韦；格卡瑞韦
• 英文名称: glecaprevir
• 英文别名: ABT-493；(1R,14E,18R,22R,26S,29S)-26-tert-butyl-N-[(1R,2R)-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
• CAS: 1365970-03-1
• 化学式: C₃₈H₄₆F₄N₆O₉S
• 分子量: 838.878
• InChiKey: MLSQGNCUYAMAHD-ITNVBOSISA-N

物化性质

• 熔点：
  >186°C (dec.)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

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

代谢

Glecaprevir在体外经历有限的次级代谢，主要由CYP3A酶进行。

Glecaprevir undergoes limited secondary metabolism in vitro, predominantly by CYP3A.

来源:DrugBank

毒理性

• 毒性总结

Glecaprevir根据体外或体内研究未显示具有基因毒性。在啮齿动物研究中，它也显示出对交配、雌性或雄性生育能力或早期胚胎发育没有影响。尚未进行Glecaprevir的致癌性研究。

Glecaprevir is not shown to be genotoxic according to *in vitro* or *in vivo* studies. It also shows to have no effect on mating, female or male fertility, or early embryonic development in rodent studies. Carcinogenicity studies with glecaprevir have not been conducted.

来源:DrugBank

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，仅有罕见的情况是晚期出现新的ALT或AST升高，这些升高通常是轻到中度的，并且不到1%的受试者升高超过上限正常值(ULN)的5倍。此外，Mavyret在治疗有预先存在肝硬化的患者期间，没有与肝功能失代偿的情况相关联，也没有与慢性乙型肝炎的再激活相关联，这是与其他治疗慢性丙型肝炎的口服方案相关联的两个严重并发症。然而，Mavyret尚未批准用于有晚期肝硬化（Child B级或C级）的患者，其在普通实践中的总体使用也受到限制。尽管如此，Mavyret的产品标签上有一个黑框警告，提示可能再激活乙型肝炎，推荐在开始治疗前进行HBsAg和抗-HBc的筛查，如果这些标志物存在，则需要仔细监测。

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

毒理性

• 蛋白质结合

皮布伦他韦与人体血浆蛋白的结合率约为97.5%。血液与血浆的比例大约为0.57。

Pibrentasvir is 97.5% bound to human plasma proteins. The Blood-to-plasma ratio is approximately 0.57.

来源:DrugBank

吸收、分配和排泄

• 吸收

在健康受试者中，达到血浆峰浓度（Tmax）的时间大约为5小时。非肝硬化丙型肝炎感染受试者的平均血浆峰浓度（Cmax）为597ng/mL。与空腹状态相比，进食可以提高glecaprevir的吸收率83-163%。

In healthy subjects, the time it takes to reach the peak plasma concentration (Tmax) is approximately 5 hours. The mean peak plasma concentration (Cmax) is 597ng/mL in non-cirrhotic HCV-infected subjects. Relative to fasting conditions, the consumption of meals increases the absorption of glecaprevir by 83-163%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

药物的主要消除途径是胆汁-粪便，其中92.1%的给药药物通过粪便排出，0.7%的药物通过尿液排出。

The predominant route of elimination of the drug is biliary-fecal, where 92.1% of administered drug is excreted in feces and 0.7% of the drug is excreted in the urine.

来源:DrugBank

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为产物：
  描述：

  ethyl 3,3-difluoro-2-oxopent-4-enoate 在 盐酸 、 氯化亚砜 、 2-羟基吡啶-N-氧化物 、 詹氏催化剂 、 水 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、