1-Amino-3-(3-chloro-4-fluorophenyl)urea | 1094769-79-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-Amino-3-(3-chloro-4-fluorophenyl)urea
• CAS: 1094769-79-5
• 化学式: C₇H₇ClFN₃O
• 分子量: 203.603
• InChiKey: GEQIYYWEOGGMCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 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：
  67.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Amino-3-(3-chloro-4-fluorophenyl)urea 在 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 4-(3-chloro-4-fluorophenyl)-2,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  鉴定基于 2,4,5-三取代-2,4-二氢-3H-1,2,4-三唑-3-一的小分子作为选择性 BRD9 结合剂

  摘要：

  靶向含溴结构域蛋白 9 (BRD9) 代表了开发具有抗癌特性的新药物的有前途的策略。为此，采用依赖于计算机研究的组合方法研究了一组基于 2,4,5-三取代-2,4-二氢-3 H -1,2,4-三唑-3-酮的化合物、化学合成、生物物理和生物学评价最有前途的项目。该协议最初基于分子对接实验，计算了一个包含 1896 个可能可合成的项目的库，这些项目是在计算机上针对 BRD9 的溴域进行测试的。第一组 21 种化合物 ( 1 – 21) 被选中，并通过 AlphaScreen 分析评估了 BDR9 上的结合。获得的结果表明，化合物17和20能够在亚微摩尔范围内结合 BRD9（分别为 IC 50  = 0.35 ± 0.18 μM 和 IC 50  = 0.14 ± 0.03 μM），当针对另外九个溴结构域进行测试时显示出有希望的选择性特征。利用基于 3D 结构的药效团模型，在计算机中选择了另外

  DOI：

  10.1016/j.ejmech.2022.115018
• 作为产物：
  描述：

  苯基(3-氯-4-氟苯基)氨基甲酸酯 在 一水合肼 作用下， 以 乙二醇二甲醚 为溶剂， 反应 24.0h， 生成 1-Amino-3-(3-chloro-4-fluorophenyl)urea
  参考文献：
  名称：

  Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism

  摘要：

  The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.019

文献信息

• Synthesis, Anticancer Activity, and In Silico Studies of 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine Analogs
  作者：Mohamed Jawed Ahsan、Krishna Gautam、Amena Ali、Abuzer Ali、Abdulmalik Saleh Alfawaz Altamimi、Salahuddin、Manal A. Alossaimi、S. V. V. N. S. M. Lakshmi、Md. Faiyaz Ahsan

  DOI：10.3390/molecules28196936

  日期：——

  In the current study, we described the synthesis of ten new 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine analogs (4a–j), as well as their characterization, anticancer activity, molecular docking studies, ADME, and toxicity prediction. The title compounds (4a–j) were prepared in three steps, starting from substituted anilines in a satisfactory yield, followed by their characterization via spectroscopic

  在当前的研究中，我们描述了十种新的 5-(3-溴苯基)-N-芳基-4H-1,2,4-三唑-3-胺类似物 (4a–j) 的合成及其表征，抗癌活性、分子对接研究、ADME 和毒性预测。标题化合物 (4a-j) 分三步制备，从取代苯胺开始，产率令人满意，然后通过光谱技术进行表征。按照美国国家癌症研究所 (NCI US) 的方案，测试了浓度为 10−5 M 时化合物 (4a–j) 对 9 组 58 种癌细胞系的抗癌活性，以及​​生长百分比 (GP) 和百分比计算生长抑制（PGI）。一些化合物对一些癌细胞系表现出显着的抗癌活性。CNS 癌细胞系 SNB-75 的 PGI 为 41.25%，被发现是对测试化合物 4e 最敏感的癌细胞系。发现化合物 4i 的平均 GP 是该系列化合物中最有前途的。被发现对化合物 4i 最敏感的五种癌细胞系是 SNB-75、UO-31、CCRF-CEM、EKVX 和 OVCAR-5；这五种细胞系在
• Synthesis of New 4′-(Substituted phenyl)spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones as Antimicrobial, Antitubercular, and Antifungal Agents: An Insight into the ADME and Toxicity Prediction as well as in-silico Molecular Docking Studies
  作者：Mohamed Jawed Ahsan、Abuzer Ali、Amena Ali、Obaid Afzal、Salahuddin、Mohammad Yusuf、Abdulmalik Saleh Alfawaz Altamimi、Omprakash Sharma、Manal A. Alossaimi、Md Afroz Bakht

  DOI：10.1016/j.molstruc.2023.135846

  日期：2023.10

  biologically active compounds. The synthesis of the 4′-(substitutedphenyl)spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones (3a-d) described here was quick and efficient, and it produced excellent yields. The synthesis was carried out in a hydro-alcoholic (EtOH:H2O; 1:2 v/v) system with an addition of 30% mol of boric acid in glycerol. The structure of the prepared compounds was validated using

  螺环化合物是一类重要的天然材料，以其突出的生物学特性而著称。螺[吲哚-噻唑烷]类似物在生物活性化合物的开发中有着广泛的应用。此处描述的 4'-(取代苯基)螺[二氢吲哚-3,3'-[1,2,4]三唑烷]-2,5'-二酮 ( 3a-d ) 的合成快速高效，它产生优良的产量。合成在氢醇（EtOH:H 2 O；1:2 v/v）系统中进行，并添加了 30% mol 硼酸的甘油溶液。所制备化合物的结构使用红外 (IR)、核磁共振 ( 1 H & 13C NMR) 和质谱 (GC-MS) 数据，然后是它们的抗菌、抗结核和抗真菌活性。在该系列中，4-(3-chloro-4-fluorophenyl)spiro[indoline-3,3-[1,2,4]triazolidine]-2,5-dione ( 3d )被发现是最有效的，与对革兰氏阳性（枯草芽孢杆菌和金黄色葡萄球菌）和革兰氏阴性（大肠杆菌和铜绿假单胞菌）细菌菌株的最低抑菌浓度
• Discovery of novel antitubercular 1,5-dimethyl-2-phenyl-4-([5-(arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol-3-one analogues
  作者：Mohamed Jawed Ahsan、Jeyabalan Govinda Samy、Chandra Bhushan Jain、Kunduri Rajeswar Dutt、Habibullah Khalilullah、Md. Shivli Nomani

  DOI：10.1016/j.bmcl.2011.12.014

  日期：2012.1

  In search of potential therapeutics for tuberculosis, we describe herewith the synthesis, characterization and antimycobacterial activity of 1,5-dimethyl-2-phenyl-4-([5-(arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol-3-one analogues. Among the synthesized compounds, 4-1(5-1( 4-fluorophenylamino[-1,3,4-oxadiazol-2-yl)methylamino]-1,2-dihydro-1,5-dimethyl-2-Phenylpyrazol-3-one (4a) was found to be the most promising compound active against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentrations, 0.78 and 3.12 mu g/mL, respectively, free from any cytotoxicity (>62.5 mu g/mL). (C) 2011 Elsevier Ltd. All rights reserved.
• POMA analyses as new efficient bioinformatics’ platform to predict and optimise bioactivity of synthesized 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues
  作者：Mohamed Jawed Ahsan、Jeyabalan Govindasamy、Habibullah Khalilullah、Govind Mohan、James P. Stables、Christophe Pannecouque、Eric De Clercq

  DOI：10.1016/j.bmcl.2012.09.108

  日期：2012.12

  A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC50 > 4.83 mu M and CC50 4.83 mu M. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 mu g/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2-4 mu g/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25-0.5 h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity. (C) 2012 Elsevier Ltd. All rights reserved.
• Design, synthesis and antimycobacterial evaluation of novel 3-substituted-N-aryl-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide analogues
  作者：Mohamed Jawed Ahsan、Jeyabalan Govinda Samy、Kunduri Rajeswar Dutt、Uttam K. Agrawal、Bhawani Shankar Yadav、Swati Vyas、Ravinder Kaur、Garima Yadav

  DOI：10.1016/j.bmcl.2011.06.018

  日期：2011.8

  In the present investigation, a series of 3-substituted-N-aryl-6,7-dimethoxy-3a, 4-dihydro-3-Hindeno[1,2-c]pyrazole-2-carboxamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed moderate to high inhibitory activities against Mycobacterium tuberculosis H(37)Rv and INH resistant M. tuberculosis. The compound N,3-bis(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c] pyrazole-2-carboxamide (4c) was found to be the most promising compound active against M. tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis with minimum inhibitory concentration 0.78 mu M. (C) 2011 Elsevier Ltd. All rights reserved.