oxaliplatin

• 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: oxaliplatin
• 英文别名: [(1R,2R)-2-azanidylcyclohexyl]azanide;oxalate;platinum(4+)
• 化学式: C₈H₁₂N₂O₄Pt
• 分子量: 395.274
• InChiKey: DWAFYCQODLXJNR-BNTLRKBRSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -1.11
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  6

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：大多数来源认为，接受抗癌治疗的母亲不应哺乳，尤其是使用诸如奥沙利铂等烷化剂。在一项患者中，发现最后一次给药后至少65天母乳中仍有铂。尚不清楚可能排入母乳中的铂的确切形式和毒性。哺乳婴儿会口服而非静脉注射任何铂化合物，婴儿对口服铂化合物的吸收情况尚不清楚。化疗可能对母乳的 normal microbiome 和化学成分产生不利影响。怀孕期间接受化疗的妇女更可能有哺乳困难。制造商建议，在接受奥沙利铂注射治疗期间以及最后一次给药后3个月内，妇女不应哺乳，这与一名患者乳汁中发现铂的发现一致。 ◉ 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。 ◉ 对泌乳和母乳的影响：在一项中心对74名在怀孕第二或第三季度接受癌症化疗的妇女进行电话随访研究，以确定她们产后是否成功哺乳。只有34%的妇女能够完全母乳喂养她们的婴儿，而66%的妇女报告遇到哺乳困难。与此相比，22名在怀孕期间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相关性包括：1. 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. 哺乳困难的母亲在怀孕期间平均提前3.4周接受了第一次化疗周期。在接受了含有类似药物顺铂方案的3名妇女中，有1人遇到哺乳困难。

◉ Summary of Use during Lactation:Most sources consider that mothers receiving antineoplastic therapy should not breastfeed, especially with alkylating agents such as oxaliplatin. In one patient, platinum was found in breastmilk for at least 65 days after her last dose. The exact form and toxicity of platinum that might be excreted into breastmilk are not known. The nursing infant would receive any platinum compounds orally rather than intravenously and oral absorption of oral platinum compounds by infants is not known. 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. The manufacturer recommends that women should not breastfeed during treatment with oxaliplatin injection and for 3 months after the final dose, which is consistent with findings of platinum in the milk of one patient. ◉ 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：

  oxaliplatin 在 a-无水葡萄糖酯 作用下， 以 水 为溶剂， 生成 草酸
  参考文献：
  名称：

  Stable oxaliplatin formulation

  摘要：

  公开号：

  EP1776947B1
• 作为产物：
  描述：

  cis-dichloro-(trans-1R,2R-cyclohexanediamine)platinum(II) 、 cesium oxalate 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以25%的产率得到oxaliplatin
  参考文献：
  名称：

  [EN] PREPARATION OF PLATINUM(II) COMPLEXES
  [FR] PREPARATION DE COMPLEXES DE PLATINE (II)

  摘要：

  这项发明涉及一种制备含有中性双齿配体的铂（II）配合物的方法，例如奥沙利铂。该方法包括将含有中性双齿配体的卤代铂配合物与草酸盐在溶剂中反应的步骤，其中溶剂中草酸盐的溶解度超过1 g/L。该发明还涉及新的铂（II）配合物。

  公开号：

  WO2006024897A1

文献信息

• 一种肉豆蔻酸钠晶型及其制备方法
  申请人：鲁南制药集团股份有限公司

  公开号：CN109020807B

  公开（公告）日：2022-06-24

  本发明属于化工制药领域，具体公开了一种肉豆蔻酸钠晶型，该晶型使用Cu‑Kα辐射以2θ角度表示的X‑射线粉末衍射(X‑RPD)在2θ＝4.8±0.2°、6.6±0.2°、7.3±0.2°和12.1±0.2°处有特征衍射峰。另外本发明还公开了该肉豆蔻酸钠晶型的制备方法，将肉豆蔻酸钠溶解于质子溶剂中，升温溶解，加入乙酸乙酯，搅拌降温，静置析晶即得该晶型。该肉豆蔻酸钠晶型为针状结晶，杂质少，纯度高，并且在制备米铂的过程中不易被包裹，使得米铂纯度更高，便于米铂的工业化生产。
• ORGANOMETALLIC COMPOUND
  申请人：Umicore AG & Co. KG

  公开号：US20180055810A1

  公开（公告）日：2018-03-01

  The present patent application relates to a novel organometallic compound, a process for the preparation thereof, and its use.

  本专利申请涉及一种新型有机金属化合物，其制备过程以及其用途。
• Process for the Preparation of an Anti-Tumor Platinum (II) - Complex
  申请人：Maikap Golak Chandra

  公开号：US20080207935A1

  公开（公告）日：2008-08-28

  We disclose here processes for making Platinum complex of general formula (I) where in, the conformation of 1,2-diaminocyclohexane is cis, trans-l or trans-d isomer and R 1 and R 2 combinedly make dicarboxylic acid having formulae (II), (III) and (IV), here in, the two carboxylic acid groups are on the same or on vicinal carbon atoms, n is zero or an integer ranging from 1 to 5 and R 3 is either hydrogen or a substituent with electron withdrawing or electron releasing effects exemplified by alkoxy, halo, and nitro groups by reacting a compound of formula M 2 PtX 4 wherein X represents halogen atom such as Cl or Br or thiocyanate with (i) 1,2-diaminocyclohexane (ii) source of silver ion selected from a silver compound containing divalent anion in presence of a corresponding carboxylic acid of formula (II) or (III) or (IV) to get the compound of formula (I), purifying the said compound by treating with alkali metal iodide and isolating the title compound by any conventional methods. The preparation of the said compound involves, for the first time, the intermediate formation of cis-Diiodo-trans-l-1,2-diaminocyclohexane platinum(II) and biscarboylato-trans-l-1,2-diaminocyclohexane platinum(II).

  我们在此披露制备一般式（I）的铂配合物的过程，其中1,2-二氨基环己烷的构象为顺式、反式-l或反式-d异构体，R1和R2组合成具有式（II）、（III）和（IV）的二羧酸，其中，两个羧酸基团在同一碳原子上或在邻位碳原子上，n为零或范围为1至5的整数，R3为氢或具有电子吸引或电子释放效应的取代基，例如烷氧基、卤素和硝基基团，通过将具有式M2PtX4的化合物与（i）1,2-二氨基环己烷（ii）银离子来源的银化合物和相应的式（II）或（III）或（IV）的羧酸在存在下进行反应，以获得式（I）的化合物，通过用碱金属碘化物处理所述化合物来纯化所述化合物，并通过任何传统方法分离所述化合物。所述化合物的制备首次涉及顺式-二碘-反式-l-1,2-二氨基环己烷铂（II）和双羧酸酯-反式-l-1,2-二氨基环己烷铂（II）的中间体形成。
• Cis-diiodo-(trans-l-1,2-cyclohexanediamine) platinum (II) complex and processes for preparing high purity oxaliplatin
  申请人：Menez Huerta Guillermo

  公开号：US20060041012A1

  公开（公告）日：2006-02-23

  The present invention is related to pure cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex, and a process of its preparation. The present invention is further related to the preparation of oxaliplatin using said cis-diiodo-(trans-L-1,2-cyclohexanediamine) Pt (II) complex.

  本发明涉及纯的顺式二碘-(反-L-1,2-环己二胺)铂(II)配合物及其制备方法。本发明还涉及使用所述顺式二碘-(反-L-1,2-环己二胺)铂(II)配合物制备奥沙利铂。
• 奥沙利铂的制备方法
  申请人：上海金和生物技术有限公司

  公开号：CN104447877A

  公开（公告）日：2015-03-25

  本发明公开了一种奥沙利铂的制备方法，其包括以下步骤：步骤一，四氯亚铂酸钾与碘化钾、(1R，2R)-环己二胺反应制得碘氨铂；步骤二，步骤一的碘氨铂与硝酸亚铜反应得到胺铂的硝酸盐中间体；步骤三，步骤二的硝酸盐中间体与草酸钠反应制得奥沙利铂。本发明可节约生产成本，降低患者的医疗费用、减少副作用，收率较高。