(2-picoloylcarbonyl)thiosemicarbazone | 4923-12-0

• 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-picoloylcarbonyl)thiosemicarbazone
• 英文别名: 2-(picolinoyl)hydrazinecarbothioamide；1-picolinoylthiosemicarbazide；1-(pyridine-2-carbonyl)-thiosemicarbazide；1-(Pyridin-2-carbonyl)-thiosemicarbazid；1--thiosemicarbazid；1-Picolinoyl-thiosemicarbazide；(Pyridine-2-carbonylamino)thiourea
• CAS: 4923-12-0
• 化学式: C₇H₈N₄OS
• 分子量: 196.233
• InChiKey: ZVWYMFPMFFKXMT-UHFFFAOYSA-N

物化性质

• 熔点：
  197-199 °C (decomp)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-picoloylcarbonyl)thiosemicarbazone 在 甲烷磺酸 、 ammonium hydroxide 作用下， 以 甲苯 、 水 为溶剂， 反应 16.0h， 以2.5 g的产率得到5-(3-吡啶基)-1,3,4-噻二唑-2-胺
  参考文献：
  名称：

  Structure–activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis

  摘要：

  A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 mu M or 0.008 mu g/mL in 7H9 media and therapeutic index of nearly similar to 300. However, 55 is rapidly metabolized by human liver microsomes (t(1/2) = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of similar to 10 (5). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.048
• 作为产物：
  描述：

  2-吡啶甲酸甲酯 在 盐酸 、 肼 作用下， 以 水 为溶剂， 生成 (2-picoloylcarbonyl)thiosemicarbazone
  参考文献：
  名称：

  N-Heterocyclic dicarboxylic acids: Broad-spectrum inhibitors of metallo-β-lactamases with co-antibacterial effect against antibiotic-resistant bacteria

  摘要：

  In an effort to identify novel, broad-spectrum inhibitors against the metallo-beta-lactamases (M beta Ls), several N-heterocyclic derivatives were tested as inhibitors of M beta Ls CcrA, ImiS, and L1, which are representative enzymes from the distinct M beta L subclasses. Three N-heterocyclic dicarboxylic acid derivatives were competitive inhibitors of CcrA and L1, exhibiting K-i values <= 2 mu M, while only 2,4-thiazolidinedicarboxylic acid (1b) was a competitive inhibitor of ImiS. Two 2-mercapto-1,3,4-thiadiazole derivatives were noncompetitive inhibitors of CcrA and ImiS, exhibiting K-i values <7 mu M; however, these same compounds did not inhibit L1. Two 2-mercapto-1,3,4-triazole derivatives were shown not to inhibit any of the tested M beta Ls. The N-heterocyclic derivatives were tested for antibacterial activity by examining the MIC values for existing antibiotics in the presence/absence of these derivatives. Consistent with the steady-state inhibition data, the inclusion of three N-heterocyclic dicarboxylic acid derivatives resulted in lower MIC values when using Escherichia coli BL21(DE3) cells containing the CcrA or L1 plasmids or Klebsiella pneumoniae (ATCC 700603), while 1b was the only dicarboxylic acid derivative to lower the MIC value of E. coli cells containing the ImiS plasmid. Inclusion of the 2-mercapto-1,3,4-thiadiazole derivatives resulted in lower MIC values for E. coli cells containing ImiS or L1 plasmids; however, these derivatives did not alter the MIC values for K. pneumoniae or E. coli cells containing the L1 plasmid. None of the N-heterocyclic derivatives affected the MIC of two methicillin resistant Staphylococcus aureus (MRSA) strains. Taken together, these studies demonstrate that N-heterocyclic dicarboxylic acids 1a-c and pyridylmercaptothiadiazoles 2a,b are good scaffolds for future broad-spectrum inhibitors of the MbLs. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.074

文献信息

• Pyridyl-1,3,4-thiadiazole; eine neue Variante der Thiadiazol-Synthese
  作者：P. Hemmerich、B. Prijs、H. Erlenmeyer

  DOI：10.1002/hlca.19580410714

  日期：——

  Thiosemicarbazones of aromatic aldehydes react with acetic anhydride to give well-defined N4,S-diacetyl derivatives, which readily undergo oxidative cyclisation to 2-aryl-4-acetamido-1,3,4-thiadiazoles. From these intermediates, aryl-thiadiazoles – especially 2-(2′-pyridyl)-1,3,4-thiadiazole, inaccessible by the common methods – can be obtained by acidic deacetylation, SANDMEYER substitution and catalytic

  芳族醛的硫代氨基甲唑酮与乙酸酐反应，得到定义明确的N 4，S-二乙酰基衍生物，该衍生物易于氧化环化成2-芳基-4-乙酰氨基-1,3,4-噻二唑。从这些中间体，可以通过酸性脱乙酰基化，SANDMEYER取代和催化脱卤来获得芳基-噻二唑，尤其是2-（2'-吡啶基）-1,3,4-噻二唑，这是常规方法难以达到的。
• Synthesis, structural characterization and thermal properties of three copper(II) complexes based on aryl hydrazide ligands
  作者：Ming-Li Liu、Jian-Min Dou、Da-Cheng Li、Da-Qi Wang、Jian-Zhong Cui

  DOI：10.1007/s11243-011-9565-0

  日期：2012.2

  and C–H···Cl hydrogen bonds. Complexes 2 and 3 have similar planar structures but different dimers formed by concomitant Cu···N and Cu···O interactions, respectively. Solvent accessible voids with a volume of 391 Å3 are included in the structure of complex 2, indicating that this complex is a potential host candidate. Thermogravimetric analysis shows that the three complexes are stable up to 100 °C.

  [Cu3L21(py)4Cl2] (1), [Cu(HL2)py] (2) 和 [Cu(HL3)py] (3), (H2L1 = 1-吡啶甲酰氨基硫脲, H3L2 = N'-(2-羟基苯亚甲基)-3-羟基-2-萘酰肼，H3L3 = 2-羟基-N'-((2-羟基-萘-1-基)亚甲基)苯甲酰肼)已制备并表征为物理化学和光谱方法以及 X 射线晶体学。配合物 1 具有中心对称结构，具有 –N–N– 桥连 Cu3 骨架。相邻分子通过 π–π 堆积相互作用、N–H…Cl 和 C–H…Cl 氢键连接成 3D 超分子框架。配合物2和3具有相似的平面结构，但分别由伴随的Cu…N和Cu…O相互作用形成的不同二聚体。体积为 391 Å3 的溶剂可及空隙包含在配合物 2 的结构中，表明该复合体是潜在的宿主候选者。热重分析表明，这三种配合物在 100 °C 下是稳定的。
• Design, synthesis, and biological evaluation of pleuromutilin derivatives containing 1,2,4‐triazole linker
  作者：Zi‐Dan Zhou、Yu‐Han Hu、Qi Wang、Heng Xu、Gao‐Lei Xi、Yan Liu、Liang Gu、Zhen Jin、You‐Zhi Tang

  DOI：10.1002/ddr.22050

  日期：——

  A series of thioether pleuromutilin derivatives containing 1,2,4-triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 μg/mL) than tiamulin (MIC = 0.5 μg/mL). The results

  设计合成了一系列C14侧链含有1,2,4-三唑的硫醚截短侧耳素衍生物。合成衍生物的体外抗菌活性实验表明，化合物72和73对MRSA最低抑菌浓度（MIC=0.0625μg/mL）的体外抗菌作用优于泰妙菌素（MIC=0.5μg/mL）。时间杀灭研究和抗生素后效应研究结果表明，化合物72能够快速抑制MRSA的生长（−2.16 log 10 CFU/mL），并表现出一定的抗生素后效应（PAE）时间（暴露于2×MIC和4×MIC） 2 小时后，针对 MRSA 的 PAE 分别为 1.30 和 1.35 小时）。此外，通过分子对接探索了化合物72与MRSA 50S核糖体之间的结合模式，化合物72与50S核糖体之间形成了5个氢键。
• 2-Amino-5-Substituted 1,3,4-Oxadiazoles and 5-Imino-2-Substituted Δ²-1,3,4-Oxadiazolines. A Group of Novel Muscle Relaxants
  作者：Harry L. Yale、Kathryn Losee

  DOI：10.1021/jm00322a007

  日期：1966.7
• Crystal structure, magnetic and optical properties of (2-picoloylcarbonyl) thiosemicarbazonatocopper(II) ([Cu3L2(H2O)2]·2ClO4·3H2O, and L=[C7H8N4OS]2−)
  作者：Wen-Shi Wu、Wen-Dan Cheng、Dong-Sheng Wu、Hao Zhang、Ya-Jing Gong、Yong Lu

  DOI：10.1016/j.inoche.2006.02.025

  日期：2006.5

  Trinuclear copper(II) complex of [Cu3L2(H2O)(2)] center dot 2ClO(4) center dot 3H(2)O was prepared by the reaction of (2-picoloylcarbonyl)thiosemicarbazone(H2L) and copper perchlorate hydrate, and the magnetic properties and absorption spectra were measured for the title compound, and the origin of third-order optical response was identified in terms of calculated results using density functional theory combined with sum-over-states methods. (C) 2006 Published by Elsevier B.V.