N-[(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 | 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: N-[(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-HDVLJZKUSA-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。...在所有研究物种中，放射性物质的排泄速度都较慢，在整个延长的收集期内，每日尿液和粪便样本中都能检测到低水平的放射性物质。尽管尿液轮廓表明存在多种代谢物（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）有关。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

卡泊芬净通过水解和N-乙酰化缓慢代谢。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(3)H卡泊芬净醋酸酯后在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，这可能是由于卡泊芬净降解为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�