2-(1-(6-chlorocoumarin-3-yl)ethylidene)-hydrazinecarbothioamide | 187404-97-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-(1-(6-chlorocoumarin-3-yl)ethylidene)-hydrazinecarbothioamide
• 英文别名: [1-(6-Chloro-2-oxochromen-3-yl)ethylideneamino]thiourea
• CAS: 187404-97-3
• 化学式: C₁₂H₁₀ClN₃O₂S
• 分子量: 295.749
• InChiKey: GHSVHXHKMGFLDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-(6-chlorocoumarin-3-yl)ethylidene)-hydrazinecarbothioamide 、 2-氯乙酰乙酸乙酯 在 sodium acetate 作用下， 以 乙醇 为溶剂， 以61%的产率得到ethyl 2-(2-(1-(6-chloro-2-oxo-2H-chromen-3-yl)ethylidene)hydrazinyl)-4-methylthiazole-5-carboxylate
  参考文献：
  名称：

  New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies

  摘要：

  Motivated by the potential anticancer activity of both coumarin and 2-aminothiazole nuclei, a new set of thiazol-2-yl hydrazono-chromen-2-one analogs were efficiently synthesized aiming to obtain novel hybrids with potential cytotoxic activity. MTT assay investigated the significant potency of all the target compounds against the human cervical cancer cell lines (HeLa cells). Cell cycle analysis showed that the representative compound 8a led to cell cycle cessation at G0/G1 phase indicating that CDK2/E1complex could be the plausible biological target for these newly synthesized compounds. Thus, the most active compounds (7c and 8a-c) were tested for their CDK2 inhibitory activity. The biological results revealed their significant CDK2 inhibitory activity with IC50 range of 0.022-1.629 nM. Moreover, RT-PCR gene expression assay showed that compound 8a increased the levels of the nuclear CDK2 regulators P21 and P27 by 2.30 and 5.7 folds, respectively. ELISA tequnique showed also that compound 8a led to remarkable activation of caspases-9 and -3 inducing cell apoptosis. QSAR study showed that the charge distribution and molecular hydrophobicity are the structural features affecting cytotoxic activity in this series. Molecular docking study for the most potent cytotoxic compounds (7c and 8a-c) rationalized their superior CDK2 inhibitory activity through their hydrogen bonding and hydrophobic interactions with the key amino acids in the CDK2 binding site. Pharmacokinetic properties prediction of the most potent compounds showed that the newly synthesized compounds are not only with promising antitumor activity but also possess promising pharmacokinetic properties.

  DOI：

  10.1016/j.bioorg.2019.01.026
• 作为产物：
  描述：

  5-氯代水杨醛 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 10.0h， 生成 2-(1-(6-chlorocoumarin-3-yl)ethylidene)-hydrazinecarbothioamide
  参考文献：
  名称：

  香豆素衍生物作为蘑菇酪氨酸酶抑制剂的生物学评价

  摘要：

  合成了一系列香豆素衍生物，并评价了它们对蘑菇酪氨酸酶双酚酶活性的抑制作用。结果表明，某些合成的化合物表现出显着的抑制活性。尤其是带有巯基-氨基脲基的2-（1-（香豆素-3-基）亚乙基）肼甲硫代酰胺对IC 50的酪氨酸酶抑制作用最强。值为3.44μM。对2-（1-（香豆素-3-基）-亚乙基）肼甲硫代酰胺和2-（1-（6-氯香豆素-3-基）亚乙基）-肼甲硫代酰胺的抑制机理分析表明，该化合物对甲壳素具有抑制作用。酪氨酸酶是不可逆的。初步结构活性关系（SAR）分析表明，此类化合物的进一步开发可能会引起人们的兴趣。

  DOI：

  10.1016/j.foodchem.2012.07.055

文献信息

• Various coordination behavior of coumarin appended Schiff bases towards Ruthenium(II) ion: Synthesis, spectral characterization and biological evaluation
  作者：Giriraj Kalaiarasi、Pathinathan Senthilrajkapoor、Ramasamy Indumathy

  DOI：10.1016/j.inoche.2022.109986

  日期：2022.11

  with [RuHCl(CO)(PPh3)3]. The newly synthesized complexes were characterized by elemental analysis, FT-IR, UV–Vis, 1H NMR, 13C NMR, thermal analysis, mass and X-ray diffraction techniques. From the spectral data we revealed that the ligands coordinated to the metal in a tridentate dibasic manner through pyrone carbon, azomethine nitrogen and thiolate sulphur (CNS-) in complexes Ru 2 and Ru 4, tridentate

  3-乙酰基-6-氯-2H-色烯-2-酮-氨基脲HL 1 、 3-乙酰基-6-氯-2H-色烯-2-直接反应合成了四种新型有机金属二价钌(II)配合物one-thiosemicarbazone HL 2 , 3-acetyl-7-hydroxy-2H-chromen-2-one-semicarbazone HL 3 , 3-acetyl-7-hydroxy-2H-chromen-2-one- thiosemicarbazone HL 4 with [RuHCl(CO )(PPh 3 ) 3 ]。新合成的配合物通过元素分析、FT-IR、UV-Vis、1 H NMR、13C NMR、热分析、质量和 X 射线衍射技术。从光谱数据中我们发现，配合物Ru 2和Ru 4中的配体通过吡喃酮碳、偶氮甲碱氮和硫醇硫(CNS - ) 以三齿二元方式与金属配位，通过内酯氧、偶氮甲碱氮和烯醇化物以三齿一元方式配位。络合物Ru
• Gireesh, Tegginamath; Khan, Gouse Mohiddin Z.; Kamble, Ravindra R., Journal of the Indian Chemical Society, 2011, vol. 88, # 9, p. 1459 - 1463
  作者：Gireesh, Tegginamath、Khan, Gouse Mohiddin Z.、Kamble, Ravindra R.

  DOI：——

  日期：——
• Biological evaluation of coumarin derivatives as mushroom tyrosinase inhibitors
  作者：Jinbing Liu、Fengyan Wu、Lingjuan Chen、Liangzhong Zhao、Zibing Zhao、Min Wang、Sulan Lei

  DOI：10.1016/j.foodchem.2012.07.055

  日期：2012.12

  series of coumarin derivatives were synthesised and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that some of the synthesised compounds exhibited significant inhibitory activities. Especially, 2-(1-(coumarin-3-yl)ethylidene)hydrazinecarbothioamide bearing thiose-micarbazide group exhibited the most potent tyrosinase inhibitory activity

  合成了一系列香豆素衍生物，并评价了它们对蘑菇酪氨酸酶双酚酶活性的抑制作用。结果表明，某些合成的化合物表现出显着的抑制活性。尤其是带有巯基-氨基脲基的2-（1-（香豆素-3-基）亚乙基）肼甲硫代酰胺对IC 50的酪氨酸酶抑制作用最强。值为3.44μM。对2-（1-（香豆素-3-基）-亚乙基）肼甲硫代酰胺和2-（1-（6-氯香豆素-3-基）亚乙基）-肼甲硫代酰胺的抑制机理分析表明，该化合物对甲壳素具有抑制作用。酪氨酸酶是不可逆的。初步结构活性关系（SAR）分析表明，此类化合物的进一步开发可能会引起人们的兴趣。
• New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies
  作者：Somaia S. Abd El-Karim、Yasmin M. Syam、Ahmed M. El Kerdawy、Tamer M. Abdelghany

  DOI：10.1016/j.bioorg.2019.01.026

  日期：2019.5

  Motivated by the potential anticancer activity of both coumarin and 2-aminothiazole nuclei, a new set of thiazol-2-yl hydrazono-chromen-2-one analogs were efficiently synthesized aiming to obtain novel hybrids with potential cytotoxic activity. MTT assay investigated the significant potency of all the target compounds against the human cervical cancer cell lines (HeLa cells). Cell cycle analysis showed that the representative compound 8a led to cell cycle cessation at G0/G1 phase indicating that CDK2/E1complex could be the plausible biological target for these newly synthesized compounds. Thus, the most active compounds (7c and 8a-c) were tested for their CDK2 inhibitory activity. The biological results revealed their significant CDK2 inhibitory activity with IC50 range of 0.022-1.629 nM. Moreover, RT-PCR gene expression assay showed that compound 8a increased the levels of the nuclear CDK2 regulators P21 and P27 by 2.30 and 5.7 folds, respectively. ELISA tequnique showed also that compound 8a led to remarkable activation of caspases-9 and -3 inducing cell apoptosis. QSAR study showed that the charge distribution and molecular hydrophobicity are the structural features affecting cytotoxic activity in this series. Molecular docking study for the most potent cytotoxic compounds (7c and 8a-c) rationalized their superior CDK2 inhibitory activity through their hydrogen bonding and hydrophobic interactions with the key amino acids in the CDK2 binding site. Pharmacokinetic properties prediction of the most potent compounds showed that the newly synthesized compounds are not only with promising antitumor activity but also possess promising pharmacokinetic properties.