cis-Pt[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]I₂

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧戊环
• 英文名称: cis-Pt[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]I₂
• 英文别名: [(4R,5R)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine;diiodoplatinum
• 化学式: C₈H₁₈I₂N₂O₂Pt
• 分子量: 623.132
• InChiKey: DKSKQKXXFHQXRW-YFJLMHTMSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  1.44
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  70.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(nitrooxy)acetic acid 、 cis-Pt[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]I₂ 在 silver nitrate 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 48.0h， 以36.9%的产率得到
  参考文献：
  名称：

  一氧化氮供体基铂配合物作为潜在的抗癌药

  摘要：

  结合力：研究了含有有机硝酸盐配体的铂络合物作为抗癌剂。该复合物在水溶液中稳定，显示出优于相应母体化合物（卡铂）的细胞毒性，因此表明硝酸盐基配体释放一氧化氮的能力与铂的能力之间存在有趣的协同作用。抑制DNA合成的部分（请参阅方案）。

  DOI：

  10.1002/chem.201201605
• 作为产物：
  描述：

  potassium tetraiodoplatinate 、 (4R,5R)-4,5-双(氨基甲基)-2-异丙基-1,3-二氧戊环 以 水 为溶剂， 反应 4.0h， 以6.8 g的产率得到cis-Pt[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]I₂
  参考文献：
  名称：

  Synthesis and anticancer activity of a new water-soluble derivative of heptaplatin, cis-{Pt(II)[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane](3-acetoxyl-cyclobutane-1,1-dicarboxylato)}

  摘要：

  一种新型水溶性七铂衍生物，顺式-{Pt(II)[(4R,5R)-4,5-双(氨甲基)-2-异丙基-1,3-二氧戊环](3-乙酰氧基-环丁烷-1) ,1-二羧基)}已合成，通过元素分析、MS、IR和 1H、13C NMR 进行表征，并评估了四种人类癌细胞系的体外抗癌活性。还通过监测 D2O 中 1H NMR 的变化研究了衍生物在水中的稳定性。结果表明，该新衍生物在水中具有良好的溶解度和稳定性，对胃癌细胞、卵巢癌细胞和结肠癌细胞也表现出较高的抗癌活性。因此，其体内抗肿瘤活性和毒性值得进一步评价。

  DOI：

  10.1007/s11164-014-1728-0

文献信息

• Synthesis and anticancer activity of diam(m)ine platinum(II) complexes with 3-oxo-cyclobutane-1,1-dicarboxylate as the leaving group
  作者：Wen Tian、Ling He

  DOI：10.1007/s11164-015-1924-6

  日期：2015.11

  Four water-soluble dia(m)mine platinum complexes with 3-oxo-cyclobutane- 1,1-dicarboxylate as the leaving group have been synthesized. These compounds were evaluated for their in vitro anticancer activity against three human A549, SK-OV-3, and HT-29 cancer cell lines. All the tested compounds showed potent activity in lung carcinoma (A549), ovarian carcinoma (SK-OV-3), and colon cancer cell (HT-29) lines. Complex 2(IC50 value = 1.57 µM for A549 and IC50 value = 0.88 µM for HT-29 cells) and Complex 4 (IC50 value = 15.3 µM for SK-OV-3 cells) displayed the most potent anticancer activity of the series. Also, preliminary acute toxicity of the platinum complexes derivatives has shown the same level as carboplatin and lower toxicity than cisplatin in vivo. All the complexes were characterized by elemental analysis as well as by ESI+-MS, FT-IR, 1H- and 13C-NMR, and have shown a satisfactory water solubility.

  我们合成了四种以 3-oxo-cyclobutane- 1,1-dicarboxylate 为离去基团的水溶性二(m)矿铂配合物。对这些化合物针对三种人类 A549、SK-OV-3 和 HT-29 癌细胞系的体外抗癌活性进行了评估。所有测试化合物对肺癌（A549）、卵巢癌（SK-OV-3）和结肠癌细胞系（HT-29）都显示出了强大的活性。复合物 2（对 A549 细胞的 IC50 值为 1.57  =  µM，对 HT-29 细胞的 IC50 值为 0.88  µM）和复合物 4（对 SK-OV-3 细胞的 IC50 值为 15.3  µM）显示出该系列化合物中最强的抗癌活性。此外，铂络合物衍生物的初步急性毒性与卡铂相同，体内毒性低于顺铂。所有复合物都通过元素分析、ESI+-MS、傅立叶变换红外光谱、1H-和 13C-NMR 进行了表征，并显示出令人满意的水溶性。
• Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate
  作者：Weiping Liu、Jing Jiang、Yongping Xu、Shuqian Hou、Liping Sun、Qingsong Ye、Liguang Lou

  DOI：10.1016/j.jinorgbio.2015.02.002

  日期：2015.5

  study belong to the carriers of six clinically approved platinum drugs. Among the complexes synthesized, complex 2, cis-[Pt(II)(1R,2R-diaminocyclohexane)·(3-dichoroacetoxylcyclobutane-1,1-dicarboxylate)] is the most promising in terms of water solubility and potential of being totally devoid of cross-drug resistance with cisplatin. Therefore, complex 2 was selected for the dichloroacetate release test

  合成了四个新的二胺（m）ine铂配合物，它们含有3-二氯乙酰氧基环丁烷-1,1-二羧酸酯中的二氯乙酸酯部分作为离去基团，通过元素分析以及ESI + -MS（电喷雾电离质谱在正模式下）进行表征），FT-IR，1 H和13 C-NMR，并评价它们的体外抗人肺癌细胞系（A549）和卵巢癌细胞系（SK-OV-3，SK-OV-3的抗癌活性/ DDP）。本研究中使用的Diam（m）ines属于六种临床批准的铂类药物的载体。之间的复杂合成的复合物，2，顺式- [铂（II）（1R，2R就水溶性和完全不具有与顺铂的交叉耐药性的潜力而言，-（二氨基环己烷）·（3-二氯乙酰氧基环丁烷-1，1-二羧酸酯）]是最有前途的。因此，选择复合物2用于二氯乙酸盐释放测试。该测试表明，在生理条件下，通过将二氯乙酸酯部分和铂药效团桥接在一起的酯键的水解，二氯乙酸酯可以有效地从复合物2中释放出来。我们的研究支持对该复合物作为候选药物的进一步评估。
• 一种含三氟甲基的铂类抗肿瘤化合物及其制备方法和应用
  申请人：浙江工业大学

  公开号：CN115181134A

  公开（公告）日：2022-10-14

  本发明公开了一种含三氟甲基的铂类抗肿瘤化合物及其制备方法和应用，该化合物的结构式如式(Ⅰ)所示，其中式(Ⅰ)中的Am为氨基载体配体，取代基R1取代或不取代，R1为羟基、氨基、三氟甲基、糖基、连接有生物活性化合物的酯键、连接有生物活性化合物的酰胺键或连接有生物活性化合物的醚键。本发明的化合物体外对肺癌细胞A549、肝癌细胞HepG2、乳腺癌细胞MCF‑7和人结肠癌细胞HCT‑116的生长均有明显的抑制作用，抗癌活性大于卡铂，其中个别化合物的抗肿瘤活性优于奥沙利铂，与顺铂相近，并且对于正常肺上皮细胞BEAS‑2B的细胞毒活性较小，具有良好的临床应用前景。
• Antitumor Platinum(II) Complexes Containing Platinum-Based Moieties of Present Platinum Drugs and Furoxan Groups as Nitric Oxide Donors: Synthesis, DNA Interaction, and Cytotoxicity
  作者：Jian Zhao、Shaohua Gou、Yanyan Sun、Lei Fang、Zhimei Wang

  DOI：10.1021/ic301374z

  日期：2012.10.1

  Six novel platinum(II) complexes 1-6 bearing different furoxan moieties as nitric oxide (NO) donors have been designed, synthesized, and characterized by elemental analysis and H-1 NMR, IR, and ESI-MS spectroscopy. The furoxan groups were introduced to the platinum complexes to release NO, which may take synergic action with the platinum-based moieties on the tumor cells. It was found that all compounds exhibited considerable cytotoxicity against human HCT-116 and SGC-7901 cell lines via DNA binding together with NO-releasing features, especially for compound 3. This finding is in accordance with the previous reports that NO hybrids show higher cytotoxicity against colon cancer cell lines compared with their parent compounds.
• Synthesis, anticancer activity and toxicity of a water-soluble 4S,5S-derivative of heptaplatin, cis-{Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]·(3-hydroxyl-cyclobutane-1,1-dicarboxylate)}
  作者：Weiping Liu、Jing Jiang、Chengying Xie、Shuqian Hou、Haitian Quan、Qingsong Ye、Liguang Lou

  DOI：10.1016/j.jinorgbio.2014.07.013

  日期：2014.11

  A water-soluble 4S,5S-derivative of heptaplatin, cis-Pt(II)[(4S,5S)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]center dot(3-hydroxyl-cyclobutane-1,1-dicarboxylate)} was synthesized. The anticancer activity and toxicity were evaluated by comparing its interaction with DNA, cytotoxicity against four human cancer cell lines, antitumor efficiency in human gastric carcinoma NCI-N87 xenografts in nude mice, and preliminary side-effects in rats to those of its 4R,5R-optical isomer which is under preclinical development. Both isomers induce condensation of DNA to the same extent and have similar cytotoxicity, but show different antitumor activity and toxicity, probably owing to the difference in respective pharmacokinetic profiles. 4S,5S-Isomer seems to exhibit superior antitumor activity and less toxicity than 4R,5R-optical isomer as well as the parent heptaplatin. These results imply that 4S,5S-configuration as a new drug candidate may be better than 4R,5R-counterpart. (C) 2014 Elsevier Inc. All rights reserved.