Potassium 7-chloro-2-oxido-5-phenyl-3H-1,4-benzodiazepine-3-carboxylate--water (2/1/1) | 57109-90-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: Potassium 7-chloro-2-oxido-5-phenyl-3H-1,4-benzodiazepine-3-carboxylate--water (2/1/1)
• 英文别名: dipotassium;7-chloro-2-oxido-5-phenyl-3H-1,4-benzodiazepine-3-carboxylate;hydrate
• CAS: 57109-90-7
• 化学式: C16H11ClK2N2O4
• 分子量: 408.92
• InChiKey: QCHSEDTUUKDTIG-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4.92
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  82.6
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：氯拉卓潘被分泌入乳汁中，并似乎在哺乳婴儿的血清中积聚。由于氯拉卓潘及其活性代谢物的半衰期较长，因此相对于剂量来说，安排哺乳时间对减少婴儿接触几乎没有好处。在哺乳新生儿或早产儿时，可能更倾向于使用其他药物。如果使用氯拉卓潘，监测婴儿是否有镇静、进食不良和体重增长不良的情况。 ◉ 对哺乳婴儿的影响：在母亲使用具有活性代谢物去甲地西泮的地西泮期间，有报告称婴儿出现镇静。也有人担心去甲地西泮可能会与新生儿体内的胆红素竞争肝脏葡萄糖醛酸结合。 ◉ 对泌乳和乳汁的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Clorazepate is excreted into breastmilk and appears to accumulate in the serum of breastfed infants. Because the half-life of clorazepate and its active metabolite are long, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Other agents may be preferred, especially while nursing a newborn or preterm infant. If clorazepate is used, monitor the infant for sedation, poor feeding and poor weight gain. ◉ Effects in Breastfed Infants:Sedation in infants has been reported during maternal use of diazepam which has nordiazepam as its active metabolite. Concern has also been expressed that nordiazepam may compete with bilirubin for hepatic glucuronide conjugation in the neonate. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 肝毒性

有关氯巴占的肝毒性的数据有限。在临床试验中，与安慰剂治疗相比，氯巴占并未与血清转氨酶升高频率的增加有关联，并且没有出现临床上明显的肝损伤的实例。自从氯巴占广泛用于临床以来，没有发表过有关其肝毒性的个案报告。苯二氮䓬类药物导致肝损伤的情况相当罕见，但已经报道过氯氮䓬和氯硝西泮这两种主要用于癫痫治疗的其它苯二氮䓬类药物的肝毒性孤立实例。因此，如果氯巴占导致临床上明显的肝损伤，这种情况也一定非常罕见。

Limited data are available on the hepatotoxicity of clobazam. In clinical trials, clobazam was not associated with an increased frequency of serum aminotransferase elevations as compared to placebo treatment, and there were no instances of clinically apparent liver injury. No individual case reports of clobazam hepatotoxicity have been published since its wide spread clinical availability. Liver injury from benzodiazepines is quite rare, but isolated instances of hepatotoxicity have been reported for clorazepate and clonazepam, two other benzodiazepines used predominantly in the therapy of epilepsy. Thus, clinically apparent liver injury due to clobazam must be rare, if it occurs at all.

来源:LiverTox

毒理性

• 肝毒性

氯拉卓帕酯与其他苯二氮卓类药物一样，很少与血清ALT升高有关，且氯拉卓帕酯引起的临床上明显的肝损伤极为罕见。只有少数几个关于氯拉卓帕酯引起急性肝细胞损伤的案例报告，且这些报告的说服力有限。其他苯二氮卓类药物，如氯氮卓、地西泮、氟西泮、三唑仑和阿普唑仑，也有极少数药物诱导肝损伤的报道。在苯二氮卓类药物相关的急性肝损伤案例中，潜伏期从几周到6个月不等；典型的肝酶升高模式为胆汁淤积型或混合型，但也有肝细胞损伤模式的报道。损伤通常为轻到中度，且为自限性。未见发热和皮疹的描述，也未形成自身抗体。

Clorazepate, as with other benzodiazepines, is rarely associated with serum ALT elevations, and clinically apparent liver injury from clorazepate is extremely rare. A few only partially convincing case reports of acute hepatocellular injury from clorazepate have been reported. Rare instances of drug induced liver injury have been reported with other benzodiazepines, such as chlordiazepoxide, diazepam, flurazepam, triazolam and alprazolam. In benzodiazepine related cases of acute liver injury, the latency has ranged from a few weeks to 6 months; the typical pattern of liver enzyme elevations has been cholestatic or mixed, but instances of hepatocellular patterns have also been reported. The injury is usually mild to moderate in severity and self-limited. Fever and rash have not been described nor has autoantibody formation.

来源:LiverTox

毒理性

• 肝毒性

有关氯巴占的肝毒性的数据有限。在临床试验中，与安慰剂治疗相比，氯巴占并未与血清转氨酶升高的频率增加有关，并且没有出现临床上明显的肝脏损伤的实例。自从氯巴占广泛临床使用以来，没有发表过关于其肝毒性的个例报告。苯二氮卓类药物导致肝脏损伤的情况相当罕见，但已经报道过氯氮卓和氯硝西泮这两种主要用于癫痫治疗的苯二氮卓类药物的肝毒性孤立实例。因此，如果氯巴占导致临床上明显的肝脏损伤，这种情况也一定是罕见的，甚至可能根本不会发生。

Limited data are available on the hepatotoxicity of clobazam. In clinical trials, clobazam was not associated with an increased frequency of serum aminotransferase elevations as compared to placebo treatment, and there were no instances of clinically apparent liver injury. No individual case reports of clobazam hepatotoxicity have been published since its wide spread clinical availability. Liver injury from benzodiazepines is quite rare, but isolated instances of hepatotoxicity have been reported for clorazepate and clonazepam, two other benzodiazepines used predominantly in the therapy of epilepsy. Thus, clinically apparent liver injury due to clobazam must be rare, if it occurs at all.

来源:LiverTox

毒理性

• 肝毒性

氯拉卓酯与其他苯二氮卓类药物一样，很少与血清ALT升高有关，且氯拉卓酯引起的临床上明显的肝损伤极为罕见。仅有几份关于氯拉卓酯引起急性肝细胞损伤的部分有说服力的病例报告。其他苯二氮卓类药物，如氯氮卓、地西泮、氟硝西泮、三唑仑和阿普唑仑也有极少数药物诱导肝损伤的报道。在苯二氮卓类药物相关的急性肝损伤病例中，潜伏期从几周到6个月不等；典型的肝酶升高模式为胆汁淤积性或混合型，但也有肝细胞损伤模式的报道。损伤通常为轻到中度，且为自限性。未见发热和皮疹的描述，也未形成自身抗体。

Clorazepate, as with other benzodiazepines, is rarely associated with serum ALT elevations, and clinically apparent liver injury from clorazepate is extremely rare. A few only partially convincing case reports of acute hepatocellular injury from clorazepate have been reported. Rare instances of drug induced liver injury have been reported with other benzodiazepines, such as chlordiazepoxide, diazepam, flurazepam, triazolam and alprazolam. In benzodiazepine related cases of acute liver injury, the latency has ranged from a few weeks to 6 months; the typical pattern of liver enzyme elevations has been cholestatic or mixed, but instances of hepatocellular patterns have also been reported. The injury is usually mild to moderate in severity and self-limited. Fever and rash have not been described nor has autoantibody formation.

来源:LiverTox

反应信息

• 作为反应物：
  描述：

  Potassium 7-chloro-2-oxido-5-phenyl-3H-1,4-benzodiazepine-3-carboxylate--water (2/1/1) 、 potassium dihydrogenphosphate 在 水 作用下， 以 水 为溶剂， 反应 12.0h， 生成 去甲西泮
  参考文献：
  名称：

  Intermediates for preparing 1,4-benzodiazepine-2-ones having a

  摘要：

  用于制备具有以下式子的新型苯二氮平类化合物的中间体：##SPC1## 其中R.sub.1是氢原子、卤素原子或三氟甲基、低碳基、低氧基、硝基或氨基基团；R.sub.2是呋喃基、噻吩基、环己基、低碳基或苯基，其可以被卤素原子或三氟甲基、硝基、低碳氧基或低碳基取代；R.sub.3是氢原子或低碳基；R.sub.4是低碳基酯基、氨酰基、N-低碳基氨基甲酰基、N,N-二低碳基氨基甲酰基、N-(二低碳基氨基烷基)氨基甲酰基、具有公式--COOCat的基团，其中Cat是碱金属的阳离子或碱土金属的半阳离子或COOCat.CatOH，这些中间体是具有以下式子的邻氨基芳基酮亚胺：##SPC2## 其中R是氢原子或##EQU1## R.sub.1、R.sub.2和R.sub.3如上所定义，R.sub.4是氢原子、低碳基酯基、氨酰基、N-低碳基氨基甲酰基、N,N-二低碳基氨基甲酰基、N-(二低碳基氨基烷基)氨基甲酰基、烷基或取代烷基；R.sub.5是低碳基。

  公开号：

  US03966793A1