Caspofungin | 162808-62-0

• 物质功能分类: 原料药 - 专科用药 - 眼科用药
• 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: Caspofungin
• 英文别名: (10R,12S)-N-[(3S,6S,9S,11R,15S,18S,20R,21S,24S,25S)-21-(2-aminoethylamino)-3-[(1R)-3-amino-1-hydroxypropyl]-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,25-trihydroxy-15-[(1R)-1-hydroxyethyl]-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexazatricyclo[22.3.0.09,13]heptacosan-18-yl]-10,12-dimethyltetradecanamide
• CAS: 162808-62-0
• 化学式: C₅₂H₈₈N₁₀O₁₅
• 分子量: 1093.3
• InChiKey: JYIKNQVWKBUSNH-WVDDFWQHSA-N

物化性质

• 沸点：
  1408.1±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)
• 溶解度：
  In water, 28 mg/L at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  77
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  412
• 氢给体数：
  16
• 氢受体数：
  18

ADMET

代谢

通过水解和N-乙酰化缓慢代谢；同时发生自发的化学降解并进一步水解为构成氨基酸及其降解产物，包括二羟基同酪氨酸和N-乙酰二羟基同酪氨酸。

Slowly metabolized by hydrolysis and N-acetylation; also undergoes spontaneous chemical degradation and further hydrolysis to constitutive amino acids and their degredates, including dihydroxyhomotyrosine and N-acetyl-dihydroxyhomotyrosine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

卡泊芬净在肝脏中通过水解和N-乙酰化缓慢代谢；单次静脉注射放射性标记剂量后，分别有35%和41%的母药和代谢物通过粪便和尿液排出。

Caspofungin is slowly metabolized in the liver via hydrolysis and N-acetylation; 35 and 41% of the parent drug and metabolites were excreted in feces and urine, respectively, following a single IV radiolabeled dose.

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了小鼠、大鼠、兔和猴单次静脉注射卡泊芬净后的代谢、排泄和药代动力学。...在所有研究的物种中，放射性物质的排泄速度都较慢，在延长的收集期内，每日尿液和粪便样本中都能检测到低水平的放射性物质。尽管尿液图谱显示存在多种代谢物（M0、M1、M2、M3、M4、M5和M6），但大部分总放射性物质与极性代谢物M1[4(S)-羟基-4-(4-羟基苯基)-L-苏氨酸]和M2（N-乙酰-4(S)-羟基-4-(4-羟基苯基)-L-苏氨酸）相关。因此，卡泊芬净主要通过代谢转化消除；然而，代谢速率较慢。...

The metabolism, excretion, and pharmacokinetics of caspofungin were investigated after administration of a single intravenous dose to mice, rats, rabbits, and monkeys. ... Excretion of radioactivity in all species studied was slow, and low levels of radioactivity were detected in daily urine and fecal samples throughout a prolonged collection period. Although urinary profiles indicated the presence of several metabolites (M0, M1, M2, M3, M4, M5, and M6), the majority of the total radioactivity was associated with the polar metabolites M1 [4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine] and M2 (N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine). Caspofungin was thus primarily eliminated by metabolic transformation; however, the rate of metabolism was slow. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

醋酸卡泊芬净通过水解和N-乙酰化缓慢代谢。醋酸卡泊芬净还会自发化学降解为开环肽化合物L-747969。在较晚的时间点（≥5天剂量后），单次给药后血浆中存在低水平的（≤7皮摩尔/毫克蛋白，或≤1.3%的给药剂量）放射性标记的共价结合，这可能是由于醋酸卡泊芬净化学降解为L-747969时形成的两个反应中间体。额外的代谢涉及水解成构成氨基酸及其降解物，包括二羟基同酪氨酸和N-乙酰二羟基同酪氨酸。这两种酪氨酸衍生物仅存在于尿液中，表明这些衍生物通过肾脏快速清除。/醋酸卡泊芬净/

Caspofungin is slowly metabolized by hydrolysis and N-acetylation. Caspofungin also undergoes spontaneous chemical degradation to an open-ring peptide compound, L-747969. At later time points (> or = 5 days postdose), there is a low level (< or = 7 picomoles/mg protein, or < or = 1.3% of administered dose) of covalent binding of radiolabel in plasma following single-dose administration of (3)H caspofungin acetate, which may be due to two reactive intermediates formed during the chemical degradation of caspofungin to L-747969. Additional metabolism involves hydrolysis into constitutive amino acids and their degradates, including dihydroxyhomotyrosine and N-acetyl-dihydroxyhomotyrosine. These two tyrosine derivatives are found only in urine, suggesting rapid clearance of these derivatives by the kidneys. /Caspofungin acetate/

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 在对健康受试者进行70毫克(3)HCaspofungin醋酸盐1小时静脉输液后，药物相关物质的排泄非常缓慢，以至于在27天内，分别有41%和35%的给药放射性在尿液和粪便中回收。在给药后约24小时收集的血浆和尿液样本中，主要含有未改变的卡泊芬净醋酸盐，以及微量的肽水解产物M0，一种线性肽。然而，在后来的采样时间点，M0被证明是主要的循环成分，而相应的尿液标本主要含有水解代谢物M1和M2，以及M0和未改变的MK-0991，其在给药后前16天的累积尿排泄分别占尿放射性的13%，71%，1%和9%。主要代谢物M2在酸性条件下极性很高且极不稳定，当其转化为识别为N-乙酰-4(S)-羟基-4-(4-羟基苯基)-L-苏氨酸γ-内酯的较不极性产物时。在水中对M2进行衍生化导致其被识别为相应的γ-羟�