2-pyridineformamide hydrazone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-pyridineformamide hydrazone
• 英文别名: N³-(2-pyridoyl)-4-pyridinecarboxamidrazone；2-pyridineformamideisonicotinoyl hydrazone；N-[(Z)-[amino(pyridin-2-yl)methylidene]amino]pyridine-4-carboxamide
• 化学式: C₁₂H₁₁N₅O
• 分子量: 241.252
• InChiKey: XOVVMVNGALTNLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-pyridineformamide hydrazone 生成 3-(2-吡啶)-5-(4-吡啶)-1,2,4-三唑
  参考文献：
  名称：

  Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia

  摘要：

  Our previous study identified 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-4-pyridyl)-1H-[1,2,4]-triazol-3-yl]-benzonitrile (2) as a safe and potent xanthine oxidoreductase (XOR) inhibitor for the treatment of hyperuricemia. Here, we synthesized a series of 3,5-dipyridyl-1,2,4-triazole derivatives and, in particular, examined their in vivo activity in lowering the serum uric acid levels in rats. As a result, we identified 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole (FYX-051, compound 39) to be one of the most potent XOR inhibitors; it exhibited an extremely potent in vivo activity, weak CYP3A4-inhibitory activity and a better pharmacokinetic pro. le than compound 2. Compound 39 is currently being evaluated in a phase 2 clinical trial. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.091
• 作为产物：
  描述：

  2-氰基吡啶 、 异烟肼 在 甲醇 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 2-pyridineformamide hydrazone
  参考文献：
  名称：

  Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia

  摘要：

  Our previous study identified 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-4-pyridyl)-1H-[1,2,4]-triazol-3-yl]-benzonitrile (2) as a safe and potent xanthine oxidoreductase (XOR) inhibitor for the treatment of hyperuricemia. Here, we synthesized a series of 3,5-dipyridyl-1,2,4-triazole derivatives and, in particular, examined their in vivo activity in lowering the serum uric acid levels in rats. As a result, we identified 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole (FYX-051, compound 39) to be one of the most potent XOR inhibitors; it exhibited an extremely potent in vivo activity, weak CYP3A4-inhibitory activity and a better pharmacokinetic pro. le than compound 2. Compound 39 is currently being evaluated in a phase 2 clinical trial. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.091

文献信息

• Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents
  作者：Gisele S. S. Firmino、Marcus V. N. de Souza、Claudia Pessoa、Maria C. S. Lourenco、Jackson A. L. C. Resende、Josane A. Lessa

  DOI：10.1007/s10534-016-9968-7

  日期：2016.12

  of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC50 values (0.39-0.86 µM) are similar to those ones found for doxorubicin (0.23-0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively)

  在这项研究中，N，N，O金属螯合剂2-吡啶羧甲醛异烟酸yl（HPCIH，1）及其衍生物2-乙酰吡啶-（HAPIH 2），2-吡啶甲酰胺-（HPAmIH，3）和吡嗪甲酰胺-（HPzAmIH，4）用于合成四种铜（II）配合物，[Cu（HPCIH）Cl2]·0.4 （5），[Cu（HAPIH）Cl2]·1.25 （6），[Cu（HPAmIH）Cl2]·H2O （7）和[Cu（HPzAmIH）Cl2]·1.25 （8）。分析了化合物对结核分枝杆菌H37Rv ATCC 27294菌株和人肿瘤细胞系OVCAR-8（卵巢癌），SF-295（多形胶质母细胞瘤）和HCT-116（结肠腺癌）的作用。所有铜（II）配合物在降低HCT-116和SF-295细胞生长方面均比各自的游离hydr在5 µg / mL时更有效，而只有配合物7对OVCAR-8品系的细胞毒作用要强于其配体HPAmIH。亚微摩尔剂量
• Isomeric ligands enhance the anisotropy barrier within nine-coordinated {Dy₂} compounds
  作者：Lin Sun、Shilong Wei、Jun Zhang、Wenyuan Wang、Sanping Chen、Yiquan Zhang、Qing Wei、Gang Xie、Shengli Gao

  DOI：10.1039/c7tc02786a

  日期：——

  structure on using isomeric ligands had a significant impact on the magnetic properties of compounds 1 and 2. Magnetic studies revealed that 1 and 2 exhibit slow magnetic relaxation behaviours under a zero direct-current field exhibiting effective energy barriers (Ueff) of 53.5 K and 132.6 K, respectively, wherein compound 2 possesses the highest Ueff in nine-coordinated Dy2 compounds. Ab initio calculations

  根据异构体配体，（2,4'-Hpcad = N 3-（2-吡啶基）-4-吡啶甲酰胺基和2,3'-Hpcad = N 3-（2-吡啶基）-3-吡啶甲酰胺基），两个羧酸盐-桥接的中心对称Dy III二聚体，[Dy 2（2,4'-pcad）2（C 2 H 3 O 2）4（H 2 O）2 ]·4H 2 O（1）和[Dy 2（2,3' -pcad）2（C 2 H 3 O 2）4（H 2 O）2]（2），其中Dy III离子采用单峰方形反棱镜配位几何，但表现出不同的畸变。使用异构体配体对结构进行微调对化合物1和2的磁性能有重大影响。磁性研究表明1和2在零直流电场下表现出缓慢的磁弛豫行为，分别表现出53.5 K和132.6 K的有效能垒（U eff），其中化合物2在九配位Dy 2中具有最高的U eff化合物。从化合物2的从头算算起，得出Dy III离子周围的磁相互作用，磁轴倾角和电荷分布表明，同时优化了Dy
• Interchange between coordinated and lattice solvents generates the highest energy barrier within nine-coordinated Dy^III single molecule magnets
  作者：Lin Sun、Sheng Zhang、Zhijie Jiang、Qi Yang、Sanping Chen、Yiquan Zhang、Wenyuan Wang、Qing Wei、Gang Xie

  DOI：10.1039/c7dt02382k

  日期：——

  crucial to promote axiality to enhance easy-axis magnetic anisotropy. Two mononuclear DyIII compounds with each DyIII being nine-coordinated, namely, [(C12H10N5O)Dy(NO3)2(H2O)2]·C2H5OH (1) and [(C12H10N5O)Dy(NO3)2(C2H5OH)2]·H2O (2) (HL = N3-(2-pyridoyl)-4-pyridinecarboxamidrazone), have been prepared through controlling the amount of C2H5OH and H2O solvents. Geometry modulations were realized by interchanging

  增强轴向性以增强易轴磁各向异性至关重要。两个单核DyIII化合物，每个DyIII具有九个配位，即[（C12H10N5O）Dy（NO3）2（H2O）2]·C2H5OH（1）和[（C12H10N5O）Dy（ ）2（C2H5OH）2]· （2）（HL = N3-（2-吡啶基）-4-吡啶甲酰胺基酮），是通过控制C2H5OH和 溶剂的量制备的。通过交换配位溶剂和晶格溶剂来实现几何调制，因此更接近于1到2的带帽正方形反棱镜的构型。值得注意的是，磁性研究表明，化合物1的磁化强度没有缓慢的磁弛豫，而化合物2的单分子磁体（ SMM）在九个协调的DyIII SMM中没有最高能垒（203.11 K）的静态磁场的情况下的行为。进行了从头算的计算来阐明这种不同的性能，这表明沿磁轴的较大电荷分布和在赤道平面内的较低电荷分布的组合产生了较强的易轴配体场，从而增强了磁性能，这进一步与结构对称。此外，提出了一
• An extended supramolecular coordination compound produced from PbCl2 and N′-isonicotinoylpicolinohydrazonamide
  作者：Isabel Garcia-Santos、Tamara Iglesias-Pereiro、Elena Labisbal、Alfonso Castiñeiras、Bagher Eftekhari-Sis、Ghodrat Mahmoudi、Filip Sagan、Mariusz P. Mitoraj、Damir A. Safin

  DOI：10.1039/d3ce01066j

  日期：——

  the strength order: Pb⋯O > Pb⋯Cl > N–H⋯Cl > C–H⋯Pb > C–H⋯Cl. Cooperative action of π⋯π and N–H⋯Cl provides an extraordinary dimeric stabilization energy of about −75 kcal mol−1. Finally, an unusual C–H⋯Pb interaction was identified to be attractive despite its long distance (>3.7 Å). Methanol species is found to be engaged not only in Pb⋯O tetrel bonds, but also in hydrogen N–H⋯O bonds and untypical homopolar

  我们报道了一种杂配配合物 [PbCl 2 ( HL′ )]·MeOH ( 1 ·MeOH)，由N ′-异烟酰吡啶甲肼酰胺 ( HL ) 和 PbCl 2获得，其中HL′是HL的两性离子形式，具有质子化的 4-吡啶基和去质子化的酰胺氮原子。 Pb 2+阳离子周围的所有配位键都聚集在一个半球中，产生很大的空间间隙，这使得两个1的分子彼此非常接近，并通过两个 ∼3.41 Å 的 Pb⋯Cl tetrel 键连接。结果，形成了超分子二聚体[PbCl 2 ( HL' )] 2 ，该二聚体通过两个C-H⋯Pb抑制作用和两个C-H⋯Cl相互作用而稳定。 Pb 2+阳离子的配位层通过与甲醇氧原子形成Pb⋯O四键而完成。超分子二聚体通过π⋯π（螯合环）和π⋯π相互作用连接，产生一维超分子链，并通过N-H⋯Cl氢键加强。这些链通过一组氢键和较弱的相互作用相互连接。通过电荷和能量分解方案 ETS-NOCV 以及相互作用的量子原子
• Cytotoxicity and Leishmanicidal Activity of Isoniazid-Derived Hydrazones and 2-Pyrazineformamide Thiosemicarbazones
  作者：Raquel S. Amim、Gisele S. S. Firmino、Ana C. P. D. Rego、Adriane L. Nery、Silvia A. G. Da-Silva、Marcus V. N. de Souza、Claudia Pessoa、Jackson A. L. C. Resende、José D. Figueroa-Villar、Josane A. Lessa

  DOI：10.5935/0103-5053.20150330

  日期：——

  The isoniazid-derived hydrazones 2-pyridinecarbaldehyde-(HPCIH), 2-acetylpyridine-(HAPIH), 2-benzoylpyridine- (HBPIH), 2-pyridineformamide- (HPAmIH) and 2-pyrazineformamide-(HPzAmIH) isonicotinoyl hydrazones, as well as the pyrazinamide-derived thiosemicarbazones 2-pyrazineformamide- (HPzAm4DH), N(4)-methyl-2-pyrazineformamide- (HPzAm4M), N(4) -ethyl-2-pyrazineformamide- (HPzAm4E) and N(4)-phenyl-2-pyrazineformamide (HPzAm4Ph) thiosemicarbazones, were assayed for their action against intracellular amastigote form of Leishmania (Viannia) braziliensis strains and the glioblastoma multiforme (SF-295), colon adenocarcinoma (HCT-116), ovarian cancer (OVCAR-8) and acute myeloid leukemia (HL-60) human tumor cell lines. All compounds exhibited leishmanicidal effects, with concentrations at which 50% of parasites were inhibited (IC50) in the 10.70-18.84 mu M range. Moreover, the compounds were up to 30-fold less toxic to macrophages than to the parasites. Pyrazinamide-derived thiosemicarbazones proved to have poor activity against the tumor cell lines at 5 mu g mL(-1), whereas, in general the isoniazid-derived hydrazones presented good activity, being HAPIH and HBPIH the most potent compounds (IC50 = 0.42-1.5 mu M).