(17b)-雌甾-1,3,5(10)-三烯-3,17b-二醇双[4-[二(2-氯乙基)氨基]苯乙酸]酯 | 22966-79-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: (17b)-雌甾-1,3,5(10)-三烯-3,17b-二醇双[4-[二(2-氯乙基)氨基]苯乙酸]酯
• 中文别名: 雌二醇双[4-[二(2-氯乙基)氨基]苯乙酸]酯；(17b)-雌甾-1,3,5(10)-三烯-3,17b-二醇双[4-[二(2-氯乙基)氨基]苯
• 英文名称: Estradiol mustard
• 英文别名: [(8R,9S,13S,14S,17S)-3-[2-[4-[bis(2-chloroethyl)amino]phenyl]acetyl]oxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] 2-[4-[bis(2-chloroethyl)amino]phenyl]acetate
• CAS: 22966-79-6
• 化学式: C₄₂H₅₀Cl₄N₂O₄
• 分子量: 788.7
• InChiKey: LRSFXIJGHRPOQQ-VZRQQIPSSA-N

物化性质

• 熔点：
  52.5°C
• 沸点：
  850.8±65.0 °C(Predicted)
• 密度：
  1.30
• 物理描述：
  Estradiol mustard is an off-white powder. Insoluble in water. (NTP, 1992)
• 溶解度：
  Insoluble (NTP, 1992)
• 分解：
  When heated to decomposition it emits very toxic fumes of /chlorides & nitric oxides/

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  52
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

毒理性

• 致癌物分类

国际癌症研究机构致癌剂：雌二醇芥子

IARC Carcinogenic Agent:Oestradiol mustard

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第9卷：（1975年）一些氮芥、硫芥和硒

IARC Monographs:Volume 9: (1975) Some Aziridines, N-, S- and O-Mustards and Selenium

来源:International Agency for Research on Cancer (IARC)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……监测休克，如有必要，进行治疗……预计可能出现癫痫，如有必要，进行治疗……对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用生理盐水连续冲洗每只眼睛……不要使用催吐剂。对于摄入，如果患者能够吞咽，有强烈的干呕反射，并且不流口水，用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……在去污后，用干无菌敷料覆盖皮肤烧伤……/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常。开始静脉输液，使用D5W /SRP: "保持开放"，最低流速。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象。使用地西泮（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雌二醇芥子酸（EM）是雌二醇-17β（E2）与氮芥衍生物氯苯乙酰氯的3,17β-二酯。通过在18°C和30°C下抑制3H-E2与大鼠子宫细胞质中的结合来测试EM与细胞质雌激素受体的结合能力。在两个温度下，在大剂量的药物存在下观察到抑制曲线，表明后者具有很强的结合亲和力（比E2低100,000倍）。在存在和不存在过量的EM的情况下，用不断增加的3H-E2量孵育子宫细胞质表明，药物与E2在相同的位点与受体相互作用（竞争性抑制）。在18°C下用EM预孵育子宫细胞质导致3H-E2结合能力的逐渐降低。当从开始就在标记的E2存在下长时间孵育细胞质时，这种减少也会发生，但程度较小。该过程在18°C下比在4°C下更快，并且在使用组织匀浆缓冲液中预孵育的EM时不会发生。通过3H-E2交换实验，用标记的E2和过量的EM预孵育的子宫受体的结果表明，药物诱导的结合能力抑制是可逆的，并且没有明显改变受体。此外，交换速率与之前用未标记的E2填充的受体的观察到的速率相似。在9个人乳腺癌的“受体阳性”细胞质中，在过量的EM存在下，3H-E2结合的时间过程研究得到了与大鼠子宫细胞质相似的结果。这些结果表明，EM对雌激素受体的结合亲和力非常低，并且它被代谢成一种或几种具有更高结合亲和力的化合物。它们表明，EM可能不会在雌激素靶组织（如乳腺癌）中显著浓缩。因此，这种药物不太可能通过涉及雌激素受体浓缩的特定机制在乳腺癌治疗中具有很大价值。

Estradiol mustard (EM) is the 3,17beta-diester of estradiol-17beta (E2) with the nitrogen mustard derivative chlorphenacyl. The ability of EM to bind to cytoplasmic estrogen receptors was tested by inhibition of the binding of 3H-E2 to rat uterine cytosol at 18 degrees C and 30 degrees C. At both temperatures an inhibition curve was observed in the presence of a large excess of drug, suggesting that the latter has a very weak binding affinity (100,000 times lower than E2). Incubation of uterine cytosol with increasing amounts of 3H-E2 in the presence and absence of an excess of EM indicated that the drug interacted with the receptors at the same sites as E2 (competitive inhibition). Preincubation of uterine cytosol at 18 degrees C with EM induced a progressive reduction of 3H-E2 binding capacity. This reduction also occurred, although to a lesser extent, when long-term incubation of the cytosol with EM was performed in the presence of labelled E2 from the start. The process was faster at 18 degrees C than at 4 degrees C and did not occur with EM preincubated in homogenization buffer. Exchange assays by 3H-E2 of uterine receptors preincubated with labelled E2 and excess EM indicated that the drug-induced inhibition of binding capacity was reversible and produced no apparent alteration of the receptors. Furthermore, the rate of exchange was similar to that observed with receptors previously filled with unlabelled E2. In 9 "receptor-positive" cytosols from human breast cancers, time-course study of the binding of 3H-E2 in the presence of excess of EM yielded similar results as those obtained with rat uterine cytosol. These results show that EM has a very low binding affinity for the extrogen receptors and that it is metabolized into one or several compounds of higher binding affinity. They suggest that EM is probably not significantly concentrated by the estrogen target tissues such as mammary cancers. Therefore, the drug is unlikely to be very valuable in the treatment of breast cancer through a specific mechanism involving concentration by the estrogen receptors.

来源:Hazardous Substances Data Bank (HSDB)