1,1-cyclobutanedicarboxylate anion

• 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: 1,1-cyclobutanedicarboxylate anion
• 英文别名: cyclobutane-1,1-dicarboxylate；CBDCA-O,O'(2-)
• 化学式: C₆H₆O₄
• 分子量: 142.111
• InChiKey: CCQPAEQGAVNNIA-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期间使用总结：大多数资料认为，接受抗癌治疗的母亲不应哺乳，尤其是使用卡铂等烷化剂。在间歇性治疗期间，可能有安全的哺乳可能性，但停止哺乳的时间尚不清楚。随着化疗疗程的重复，乳汁中的铂含量可能会增加，而且不清楚排入乳汁中的铂的确切形式和毒性。哺乳婴儿会口服铂化合物，而不是静脉注射，婴儿对铂化合物的口服吸收情况尚不清楚。看起来，卡铂化疗后哺乳似乎并不安全，应停止哺乳。 化疗可能会不利地影响乳汁的正常微生物组和化学成分。在怀孕期间接受化疗的妇女更可能难以哺乳她们的婴儿。 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 对哺乳和乳汁的影响：对74名在怀孕第二或第三季度在一中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功哺乳。只有34%的妇女能够完全哺乳她们的婴儿，66%的妇女报告遇到哺乳困难。与此相比，22名在怀孕期间被诊断但未接受化疗的母亲中，有91%成功哺乳。其他具有统计学意义的关联包括：1. 有哺乳困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有哺乳困难的母亲在怀孕期间平均提前3.4周接受了第一个周期的化疗。在接受了含有类似药物顺铂方案的3名妇女中，有1名遇到哺乳困难。

◉ Summary of Use during Lactation:Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as carboplatin. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration of abstinence is not clear. Platinum in milk may increase with repeated courses of chemotherapy and the exact form(s), and toxicity of platinum excreted into breastmilk are also not known. The nursing infant would receive platinum compounds orally rather than intravenously and oral absorption of platinum compounds by infants is not known. It appears that it is not safe to breastfeed after carboplatin chemotherapy, and breastfeeding should probably be discontinued. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 3 women who received a regimen containing the similar drug, cisplatin, 1 had breastfeeding difficulties.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  乙二胺氯化铂(II) 、 1,1-cyclobutanedicarboxylate anion 在 AgNO₃ 、 NaOH 作用下， 以 水 为溶剂， 生成 ethylenediamine(1,1-cyclobutanedicarboxylato)platinum(II)
  参考文献：
  名称：

  在生理相关条件下，各种铂（II）配合物催化N-乙酰化的L-甲硫氨酰甘氨酸中酰胺键的水解

  摘要：

  可以得出结论，与相应的CBDCA Pt（II）配合物相比，在与氯化物配合物的反应中观察到MeCOMet-Gly二肽的水解裂解更快。还通过1H NMR光谱研究了Pt（II）配合物对MeCOMet-Gly二肽中酰胺键水解裂解的空间效应。已发现，水解速率随着CBDCA和氯铂Pt（II）配合物的空间体积增加而降低（en> 1,2-pn> dach）。这些结果有助于更好地理解Pt（II）抗肿瘤药物的毒副作用，在设计新的潜在的Pt（II）抗肿瘤药物（最好是低毒副作用）时应予以考虑。还通过1H NMR光谱研究了Pt（II）配合物对MeCOMet-Gly二肽中酰胺键水解裂解的空间效应。已发现，水解速率随CBDCA和氯铂Pt（II）配合物的空间体积增加而降低（en> 1,2-pn> dach）。这些结果有助于更好地理解Pt（II）抗肿瘤药物的毒副作用，在设计新的潜在的Pt（II）抗肿瘤药物（最好是低毒副作用）时应予以考虑。还通过1H

  DOI：

  10.1016/j.poly.2010.12.039

文献信息

• The interaction of [Pd(N,N-dimethylaminopropylamine)(H2O)]2+ with dicarboxylic acids and inosine: Thermodynamic model for carboplatin drug
  作者：Mohamed Shehate、Mohamed Shoukry、Mona Ragab

  DOI：10.2478/s11532-012-0053-y

  日期：2012.8.1

  The Pd(DMPA)Cl2 complex, where DMPA = N,N-dimethylaminoproylamine, was synthesized and characterized. The stoichiometry and stability constants of the complexes formed between various dicarboxylic acids and [Pd(DMPA)(H2O)2]2+ were investigated. The effect of solvent dielectric constant, chloride ion concentration of the medium and temperature on the stability constant of the cyclobutanedicaroxylic acid (CBDCA) complex was investigated. The equilibrium constants for the displacement of coordinated CBDCA by inosine, taken as an example of DNA constituents, were calculated. The results are expected to contribute to the chemistry of antitumour agents.

  摘要：合成并表征了Pd(DMPA)Cl2配合物，其中DMPA = N，N-二甲基氨基丙胺。研究了各种二羧酸和[Pd(DMPA)(H2O)2]2+之间形成的配合物的化学计量和稳定常数。研究了溶剂介电常数，介质中氯离子浓度和温度对环丁烷二羧酸（CBDCA）配合物稳定常数的影响。计算了DNA成分示例肌苷取代配位的CBDCA平衡常数。结果有望为抗肿瘤剂的化学做出贡献。