1-O-[(2S,3S)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.02,6.06,10.015,19]icosa-1(20),4,13,15(19)-tetraen-3-yl] 4-O-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 三尖杉生物碱
• 英文名称: 1-O-[(2S,3S)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.02,6.06,10.015,19]icosa-1(20),4,13,15(19)-tetraen-3-yl] 4-O-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate
• 化学式: C₂₉H₃₉NO₉
• 分子量: 545.6
• InChiKey: HYFHYPWGAURHIV-JCNWCSDUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  10

ADMET

毒理性

• 肝毒性

在对照试验中，使用奥马西汀治疗的患者的血清转氨酶升高发生在2%至6%之间，但大多数升高是轻微且短暂的，只有极少数患者需要因肝功能测试异常而调整剂量或停药。在奥马西汀的上市前试验中没有报告临床明显的肝损伤和黄疸，产品标签中也没有提及。自从奥马西汀获得批准并更广泛使用以来，没有发表或描述与使用相关的伴有黄疸的肝毒性的文献。因此，如果有的话，因奥马西汀引起的临床明显肝损伤一定很罕见。

In controlled trials, serum aminotransferase elevations occurred in 2% to 6% patients treated with omacetaxine, but most elevations were mild and transient with only rare patients requiring dose modification or discontinuation for liver test abnormalities. Clinically apparent liver injury with jaundice was not reported in the preregistration trials of omacetaxine and is not mentioned in the product label. Since the approval and more wide scale use of omacetaxine, there have been no publications or descriptions of the hepatotoxicity with jaundice associated with its use. Thus, clinically apparent liver injury due to omacetaxine must be rare, if it occurs at all.

来源:LiverTox

毒理性

毒性数据：小鼠（腹腔注射）：LD50 1960微克/千克

ToxicityData:Mouse(ip): LD50: 1960 ug/kg

来源:NCI Investigational Drugs

毒理性

毒性数据：小鼠（腹腔注射）：LD50 6.5毫克/千克

ToxicityData:Mouse(ip): LD50: 6.5 mg/kg

来源:NCI Investigational Drugs

文献信息

• METHODS AND INTERMEDIATES FOR THE PREPARATION OF OMACETAXINE AND CEPHALOTAXINE DERIVATIVES THEREOF
  申请人：ALBANY MOLECULAR RESEARCH, INC.

  公开号：US20180134724A1

  公开（公告）日：2018-05-17

  The present invention relates to methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. The resulting products are useful in the treatment of proliferative diseases and infectious diseases.