2-(1-(6-bromocoumarin-3-yl)ethylidene)hydrazinecarbothioamide | 187404-96-2

• 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-bromocoumarin-3-yl)ethylidene)hydrazinecarbothioamide
• 英文别名: [1-(6-Bromo-2-oxochromen-3-yl)ethylideneamino]thiourea
• CAS: 187404-96-2
• 化学式: C₁₂H₁₀BrN₃O₂S
• 分子量: 340.2
• InChiKey: ZHVKHBXLJAHMBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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-bromocoumarin-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66%的产率得到ethyl 2-(2-(1-(6-bromo-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-溴水杨醛 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-bromocoumarin-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

• Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives
  作者：Afsheen Arshad、Hasnah Osman、Mark C. Bagley、Chan Kit Lam、Suriyati Mohamad、Anis Safirah Mohd Zahariluddin

  DOI：10.1016/j.ejmech.2011.05.044

  日期：2011.9

  Two novel series of hydrazinyl thiazolyl coumarin derivatives have been synthesized and fully characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectral data. The structures of some compounds were further confirmed by X-ray crystallography. All of these derivatives, 10a–d and 15a–h, were screened in vitro for antimicrobial activity against various bacteria species including Mycobacterium

  已经合成了两个新颖的肼基噻唑基香豆素衍生物系列，并通过IR，1 H NMR，13 C NMR，元素分析和质谱数据进行了充分表征。X射线晶体学进一步证实了某些化合物的结构。在体外筛选了所有这些衍生物10a – d和15a – h对各种细菌（包括结核分枝杆菌和白色念珠菌）的抗菌活性。化合物10c，10d和15e 对所有测试的微生物菌株表现出非常好的活性。
• Utility of 3-Acetyl-6-bromo-2H-chromen-2-one for the Synthesis of New Heterocycles as Potential Antiproliferative Agents
  作者：Sobhi Gomha、Yasser Zaki、Abdou Abdelhamid

  DOI：10.3390/molecules201219803

  日期：——

  Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbothioamide

  含有吡唑并[1,5-a]嘧啶、四唑并[1,5-a]嘧啶、咪唑并[1,2-a]嘧啶、吡唑并[3,4-d]嘧啶、1,3,4-噻二唑的香豆素衍生物和噻唑由 6-bromo-3-(3-(二甲氨基)丙烯酰基)-2H-chromen-2-one,methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl )亚乙基)肼碳二硫代酸酯、2-(1-(6-溴-2-氧代-2H-色烯-3-基)亚乙基)肼碳硫酰胺以及杂环胺、腙酰氯和羟肟酰氯中的每一种。新合成化合物的结构是在元素分析、光谱数据和其他可能的合成路线的基础上阐明的。此外，还评估了选定的新合成产品对肝癌细胞系 (HEPG2-1) 的抗肿瘤活性。结果表明，吡唑并[1,5-a]嘧啶7c，
• Novel functionalized thiosemicarbazone ligands and their Pd(II) complexes: synthesis, characterization, antibacterial and cytotoxic activities
  作者：Safaa S. Hassan、Sobhi M. Gomha

  DOI：10.1007/s11696-018-0592-6

  日期：2019.2

  density functional theory for ligands and complexes at B3LYP functional with 6–31 ++G(d,p) basis set for ligands and LANL2DZ basis set for complexes. The charge distribution within the ligands and its pd(II) complexes was calculated using Mulliken population analysis of (MPA) and natural population analysis (NPA). The prepared pd(II) complexes showed a satisfactory cytotoxic effect results against the

  香豆素硫代半碳酰胺衍生物（1-（1-（2-oxo-2 H -chromen-3-yl）亚乙基）硫代半碳酮（OCETh），1-（1-（6-（6-溴-2-氧代- 2 H-铬-3-基）亚乙基）硫半脲（BOCETh）和1-（1-（3-氧代-3 H-苯并[ f制备了[2-亚甲基-2-铬基]亚乙基）硫半卡巴zone（NOCETh）。配合物具有式[Pd（L）Cl]。DMF，其中DMF =二甲基甲酰胺，L = OCETh，BOCETh或NOCETh。所研究的配体通过使用偶氮甲碱氮，羰基氧和硫醇硫作为供体的单阴离子中心充当三齿配体。表征部分是使用不同的物理化学工具进行的，例如元素分析，红外，可见紫外线，质量，磁测量和摩尔电导技术。理论构象结构分析是使用密度泛函理论对6–31 ++ G（d，p）配体的基础集和LANL2DZ配合物的基础集。配体及其pd（II）配合物中的电荷分布是使用（MPA）的Mulliken
• 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。