2-chloro-6-furfurylamino-9-isopropylpurine | 1239372-53-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-6-furfurylamino-9-isopropylpurine
• 英文别名: 2-chloro-N6-furfuryl-9-isopropyladenine；2-chloro-N-(furan-2-ylmethyl)-9-propan-2-ylpurin-6-amine
• CAS: 1239372-53-2
• 化学式: C₁₃H₁₄ClN₅O
• 分子量: 291.74
• InChiKey: NJOTWGPZIVUOMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  68.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  potassium tetrachloroplatinate(II) 、 2-chloro-6-furfurylamino-9-isopropylpurine 以 水 、 丙酮 为溶剂， 生成 trans-[PtCl₂(2-chloro-N6-furfuryl-9-isopropyladenine)₂]
  参考文献：
  名称：

  Dichlorido-platinum(II) complexes with kinetin derivatives as promising cytotoxic agents avoiding resistance of cancer cells: Contrasting results between cisplatin and oxaliplatin analogues

  摘要：

  With the aim to study the anticancer potential and compare the influence of different leaving groups, dichlorido and oxalato (ox) platinum(II) complexes involving di- and tri-substituted derivatives of a plant hormone kinetin (N6-furfuryladenine; L-n) were prepared: cis-[PtCl2(L-1)(2)]center dot H2O (1), trans-[PtCl2(L-1)(2)] (1a), cis-[PtCl2(L-2)(2)]center dot 0.75H(2)O (2), and [Pt(L-1)(2)(ox)] (3), [Pt(L-2)(2)(ox)] (4), with 2-chloro-N6-furfury1-9-isopropyladenine (L-1) and 2-chloro-N6-(5-methylfurfury1)-9-isopropyladenine (L-2). The complexes were structurally characterized by elemental and thermal analyses, FT-IR and H-1, C-13, N-15 and Pt-195 NMR spectroscopy, ESI+ mass spectrometry, conductivity measurements as well as single crystal X-ray diffraction (for 1). The L-n carrier ligands act as monodentate N-donors coordinated to the platinum(II) centre, which reveals a slightly distorted square-planar geometry. All the prepared complexes were screened for their in vitro cytotoxicity against breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines. This preliminary study identified only the cis-dichlorido-Pt(II) complexes 1, 2 as cytotoxic agents. These two complexes were thus further evaluated for in vitro cytotoxicity against malignant melanoma (G-361), cervix epitheloid carcinoma (HeLa), cisplatin sensitive (A2780) and resistant (A2780R) ovarian carcinoma human cancer cell lines. Most importantly, the obtained results showed that the cis-[PtCl2(L-n)(2)]center dot xH(2)O complexes were able to circumvent cisplatin resistance in A2780R cells while additionally being significantly more cytotoxic against A2780 than cisplatin, as demonstrated by the resistance factors IC50(A2780R)/IC50(A2780) equal to 0.87 for 1; 0.48 for 2 as compared to 2.25 for cisplatin. The complexes were furthermore comparably active against HOS, MCF7, G-361 cells as cisplatin. In order to address the contrasting cytotoxic results of the cisplatin (1, 2) and oxaliplatin (3, 4) analogues, their possible fate in the physiological environment, focusing on the hydrolytic stability and interactions with glutathione and 5'-guanosine monophosphate, was studied by means of H-1 NMR spectroscopy. (C) 2015 Elsevier Ltd. All rights, reserved.

  DOI：

  10.1016/j.poly.2015.01.033

文献信息

• Structurally varied Cu(II) complexes involving kinetin and its derivatives: Synthesis, characterization and evaluation of SOD-mimic activity
  作者：Radka Novotná、Radovan Herchel、Zdeněk Trávníček

  DOI：10.1016/j.poly.2011.12.016

  日期：2012.2

  Three new structural types of Cu(II) complexes of kinetin and its purine- and/or furan-substituted derivatives (HLn), involving acetato-bridges (Ac) or mixed N-donor ligands, are reported. Complexes of the compositions [Cu-2(mu(3)-L-1)(2)(mu(2)-Ac)(2)](n) (1). [Cu-2(mu(3)-L-2)(2)(mu(2)-Ac)(2)](n) (2), [Cu-2(mu(3)-L-3)(2)(mu(2)-AC)(2)](n) (3), [Cu-2(mu(2)-AC)(4)(HL5)(2)] (4), [Cu-2(mu(2)-Ac)(4)(HL6)(2)] (5), [Cu(H2O)(2)(L-3)(2)(Phen)] (6) and [Cu(H2O)(2)(L-4)(2)(Phen)]center dot 2H(2)O (7), with kinetin (N6-furfuryladenine, HL1) and its derivatives N6-(5-methylfurfuryl)adenine (HL2), 2-chloro-N6-furfuryladenine (HL3), 2-chloro-N6-(5-methylfurfuryl)adenine (HL4), 2-chloro-N6-furfury19-isopropyladenine (HL5) and 2-chloro-N6-(5-methylfurfuryl)-9-isopropyladenine (HL6) (phen = 1, 10-phenanthroline), have been fully characterized by elemental analyses, FTIR, electronic spectroscopy, conductivity, temperature dependent magnetic susceptibility measurements, thermogravimetric (TG) and differential thermal (DTA) analyses. The geometry around the Cu(II) centers is square pyramidal in the two structural groups involving the acetato bridges (1-3, and 4,5) and octahedral in the mononuclear 6 and 7. This was confirmed by single crystal X-ray analysis for the dimeric complexes 4 and 5, with each Cu(II) atom five-coordinated by four 0 atoms from the acetato bridges and one N7 atom from the adenine moiety of HLn. The length of the Cu center dot center dot center dot Cu separation present in the dimers 4 and 5 is equal to 2.6508(6) and 2.6523(4) A, respectively. The anti-radical activity of the presented complexes was evaluated by an in vitro SOD-mimic assay and the best results were found for 4 with IC50 equal to 57.41,mu M. (C) 2011 Elsevier Ltd. All rights reserved.
• Zinc(II) chlorido complexes of protonated kinetin and its derivatives: Synthesis, properties and X-ray structure of [Zn(Hkinetin)Cl3]·kinetin
  作者：Radka Novotná、Igor Popa、Zdeněk Trávníček

  DOI：10.1016/j.ica.2010.08.040

  日期：2011.1

  The syntheses and characterization of five novel zinc(II) complexes with protonated kinetin (6-furfurylaminopurine) and its derivatives are described. Based on the results following from elemental analyses (C, H, N), FTIR, Raman, H-1 and C-13 NMR spectroscopy, conductivity measurements, thermogravimetric (TG) and differential thermal analyses (DTA), and single crystal X-ray analysis, the complexes of the general composition [Zn(HLn)Cl-3]center dot xL(n) (1-5) have been prepared, where L-1 = kinetin (6-furfurylaminopurine), L-2 = 6-(5-methylfurfurylamino) purine, L-3 = 2-chloro-6-furfurylaminopurine, L-4 = 2-chloro-6-(5-methylfurfurylamino) purine and L-5 = 2-chloro-6-furfurylamino-9-isopropylpurine, and x = 1/2-2. The structure of [Zn(HL1)Cl-3]center dot L-1 (1) has been determined by single crystal X-ray analysis. The Zn(II) atom is tetrahedrally coordinated by three chlorido ligands and one N3-protonated organic molecule forming a ZnCl3N donor set. The organic ligand L-1 is coordinated to the Zn(II) centre through the N7 atom of the purine moiety. NMR spectroscopic study confirmed the N3 and N7 atom to be the protonation, and coordination site, respectively. (C) 2010 Elsevier B.V. All rights reserved.
• Synthesis and characterization of the first zinc(II) complexes involving kinetin and its derivatives: X-ray structures of 2-chloro-N6-furfuryl-9-isopropyladenine and [Zn(kinetin)2Cl2]·CH3OH
  作者：Radka Novotná、Zdeněk Trávníček、Igor Popa

  DOI：10.1016/j.ica.2010.02.004

  日期：2010.6

  A series of the first zinc(II) complexes of the general composition [Zn(L-n)(2)Cl-2]center dot xSolv (1-5) involving kinetin [N6-furfuryladenine, L-1, xSolv = CH3OH, complex 1] and its derivatives, i.e. N6-(5-methylfurfuryl)adenine (L-2, xSolv = 2H(2)O, 2), 2-chloro-N6-furfuryladenine (L-3, 3), 2-chloro-N6-(5-methylfurfuryl)adenine (L-4, 4) and 2-chloro-N6-furfuryl-9-isopropyladenine (L-5, 5), as N-donor ligands has been synthesized. The complexes have been fully characterized by elemental analyses (C, H, N), FTIR, Raman, H-1 and C-13 NMR spectroscopy, conductivity measurements, thermogravimetric (TG) and differential thermal (DTA) analyses. Single crystal X-ray analysis determined the molecular structures of 2-chloro-N6-furfuryl-9-isopropyladenine (L-5) and the complex [Zn(L-1)(2)Cl-2]center dot CH3OH. The Zn(II) ion is tetrahedrally coordinated by two chlorido ligands and two molecules of the L-1 organic compound. The two ligands L-1 are coordinated to the central Zn(II) ion via the N7 atoms. This conclusion can also be drawn from multinuclear NMR spectroscopic experiments. (C) 2010 Elsevier B.V. All rights reserved.
• Dichlorido-platinum(II) complexes with kinetin derivatives as promising cytotoxic agents avoiding resistance of cancer cells: Contrasting results between cisplatin and oxaliplatin analogues
  作者：Radka Křikavová、Lucie Hanousková、Zdeněk Dvořák、Zdeněk Trávníček

  DOI：10.1016/j.poly.2015.01.033

  日期：2015.4

  With the aim to study the anticancer potential and compare the influence of different leaving groups, dichlorido and oxalato (ox) platinum(II) complexes involving di- and tri-substituted derivatives of a plant hormone kinetin (N6-furfuryladenine; L-n) were prepared: cis-[PtCl2(L-1)(2)]center dot H2O (1), trans-[PtCl2(L-1)(2)] (1a), cis-[PtCl2(L-2)(2)]center dot 0.75H(2)O (2), and [Pt(L-1)(2)(ox)] (3), [Pt(L-2)(2)(ox)] (4), with 2-chloro-N6-furfury1-9-isopropyladenine (L-1) and 2-chloro-N6-(5-methylfurfury1)-9-isopropyladenine (L-2). The complexes were structurally characterized by elemental and thermal analyses, FT-IR and H-1, C-13, N-15 and Pt-195 NMR spectroscopy, ESI+ mass spectrometry, conductivity measurements as well as single crystal X-ray diffraction (for 1). The L-n carrier ligands act as monodentate N-donors coordinated to the platinum(II) centre, which reveals a slightly distorted square-planar geometry. All the prepared complexes were screened for their in vitro cytotoxicity against breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines. This preliminary study identified only the cis-dichlorido-Pt(II) complexes 1, 2 as cytotoxic agents. These two complexes were thus further evaluated for in vitro cytotoxicity against malignant melanoma (G-361), cervix epitheloid carcinoma (HeLa), cisplatin sensitive (A2780) and resistant (A2780R) ovarian carcinoma human cancer cell lines. Most importantly, the obtained results showed that the cis-[PtCl2(L-n)(2)]center dot xH(2)O complexes were able to circumvent cisplatin resistance in A2780R cells while additionally being significantly more cytotoxic against A2780 than cisplatin, as demonstrated by the resistance factors IC50(A2780R)/IC50(A2780) equal to 0.87 for 1; 0.48 for 2 as compared to 2.25 for cisplatin. The complexes were furthermore comparably active against HOS, MCF7, G-361 cells as cisplatin. In order to address the contrasting cytotoxic results of the cisplatin (1, 2) and oxaliplatin (3, 4) analogues, their possible fate in the physiological environment, focusing on the hydrolytic stability and interactions with glutathione and 5'-guanosine monophosphate, was studied by means of H-1 NMR spectroscopy. (C) 2015 Elsevier Ltd. All rights, reserved.