(4R,5R)-4,5-双(氨基甲基)-2-异丙基-1,3-二氧戊环 | 146092-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环氧化物
• 中文名称: (4R,5R)-4,5-双(氨基甲基)-2-异丙基-1,3-二氧戊环
• 英文名称: (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane
• 英文别名: ((4R,5R)-2-isopropyl-1,3-dioxolane-4,5-diyl)dimethanamine；[(4R,5R)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine
• CAS: 146092-05-9
• 化学式: C₈H₁₈N₂O₂
• 分子量: 174.243
• InChiKey: UUOFRXDFODYHPC-RNFRBKRXSA-N

物化性质

• 沸点：
  261.5±15.0 °C(Predicted)
• 密度：
  1.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  12
• 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：

  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
• 作为产物：
  描述：

  (4R,5R)-4,5-bis(azidomethyl)-2-isopropyl-1,3-dioxolane 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 40.0 ℃ 、344.73 kPa 条件下， 反应 2.0h， 以96%的产率得到(4R,5R)-4,5-双(氨基甲基)-2-异丙基-1,3-二氧戊环
  参考文献：
  名称：

  一系列[2-取代-4,5-双（氨基甲基）-1,3-二氧戊环]铂（II）配合物的合成和抗肿瘤活性。

  摘要：

  描述了一系列[2-取代-4,5-双（氨基甲基）-1,3-二氧戊环]铂（II）配合物的合成，物理性质，抗肿瘤活性，结构活性关系和肾毒性。已制备了该系列中具有七元环结构的42种铂（II）配合物，并通过1 H NMR，13 C NMR，IR，FAB-MS和元素分析对其进行了表征。该系列的所有成员均设计成在其载体配体中具有1,3-二氧戊环环部分以增加水溶性。铂配合物的溶解度与在4,5-双（氨基甲基）-1,3-二氧戊环载体配体中剩余配体和2-取代基的性质有关。通常，在4，5-双（氨基甲基）-1，3-二氧戊环部分中具有两个不同的R 1和R 2取代基的化合物比具有相同取代基的化合物具有更高的水溶性。该系列的大多数成员对移植到小鼠中的小鼠L1210白血病细胞显示出优异的抗肿瘤活性，并且优于顺铂和卡铂。（4R，5R）-立体异构体1a-h在（1,1-环丁烷二羧基）铂（II）配合物中比相应的（4S，5S）-立体

  DOI：

  10.1021/jm00036a013

文献信息

• Platinum(II) complex and processes for preparing the same
  申请人：Sunkyong Industries, Ltd.

  公开号：US05395947A1

  公开（公告）日：1995-03-07

  Disclosed herein are novel platinum(II) complexes having a potent anti-tumor activity which are represented by the formula (1), ##STR1## wherein R.sub.1 and R.sub.2, which may be the same or different, are a hydrogen atom or a C.sub.1-4 alkyl group, respectively, or jointly form a cycloalkane group together with the carbon atom attached thereto; two Xs jointly form a group represented by formula (a) or (b) wherein, R.sub.3 is a hydrogen atom or a methyl group; R.sub.4 and R.sub.5, which may be the same or different, are a hydrogen atom or a C.sub.1-4 alkyl group, respectively, or jointly form a cyclobutane together with the carbon thereto; and the absolute configurations at the respective chiral centers in the 4,5-bis(aminomethyl)-1,3-dioxolane moiety are (4R,5R) or (4S,5S); processes for the preparing the same; and their use for treating animal or human cancer. Further, disclosed herein are novel intermediates useful for the preparation of the platinum(II) complexes and processes for preparing said intermediates.

  本文披露了具有强效抗肿瘤活性的新型铂（II）配合物，其化学式为（1），其中R.sub.1和R.sub.2，可以相同也可以不同，分别为氢原子或C.sub.1-4烷基基团，或者与连接的碳原子共同形成环烷基基团；两个X共同形成由化学式（a）或（b）表示的基团，其中，R.sub.3为氢原子或甲基基团；R.sub.4和R.sub.5，可以相同也可以不同，分别为氢原子或C.sub.1-4烷基基团，或者与碳原子共同形成环丁烷基团；以及4,5-双(氨甲基)-1,3-二氧杂环戊烷基团中各立体中心的绝对构型为（4R,5R）或（4S,5S）；制备这些配合物的方法；以及它们用于治疗动物或人类癌症的用途。此外，本文还披露了用于制备铂（II）配合物的新型中间体以及制备这些中间体的方法。
• 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。
• 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.
• A Novel Water-Soluble Heptaplatin Analogue with Improved Antitumor Activity and Reduced Toxicity
  作者：Weiping Liu、Xizhu Chen、Qingsong Ye、Yongping Xu、Chengying Xie、Mingjin Xie、Qiaowen Chang、Liguang Lou

  DOI：10.1021/ic200436u

  日期：2011.6.20

  A novel water-soluble heptaplatin analogue, cis-[(4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3-dioxo-lane](3-hydroxy-1,1-cyclobutanedicarboxylato)platinum-(II), has been synthesized and biologically evaluated. The complex shows more activity and less toxicity than its parent drug heptaplatin, exhibiting the great potential for further development.