1-Amino-3-(3-chloro-4-methylphenyl)urea | 1100694-17-4

• 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-methylphenyl)urea
• CAS: 1100694-17-4
• 化学式: C₈H₁₀ClN₃O
• 分子量: 199.64
• InChiKey: ZUACQLWSSDXHFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Amino-3-(3-chloro-4-methylphenyl)urea 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 3.0h， 生成 4-(3-chloro-4-methylphenyl)-5-ethyl-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：

  3-氯-4-甲基苯胺 在 吡啶 、 一水合肼 作用下， 以 乙二醇二甲醚 、 乙酸乙酯 为溶剂， 反应 27.0h， 生成 1-Amino-3-(3-chloro-4-methylphenyl)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

• HETEROCYCLIC COMPOUNDS HAVING ANTITUMOR ACTIVITY
  申请人：Novuspharma S.p.A.

  公开号：EP1173420A2

  公开（公告）日：2002-01-23
• [EN] HETEROCYCLIC COMPOUNDS HAVING ANTITUMOR ACTIVITY<br/>[FR] COMPOSES HETEROCYCLIQUES AYANT UNE ACTIVITE ANTITUMORALE
  申请人：NOVUSPHARMA SPA

  公开号：WO2000053581A2

  公开（公告）日：2000-09-14

  Compounds of general formula (I) in which: Y is O, S or NH; n is 0 or 1; X is selected from the group consisting of -NH-CO-NH, -NH-CO-, NH-SO2-, -NH-, -CO-NH-, -CO-NH-NH-, -NH-NH-CO-, -NH-NH-SO2-, -NH-CO-CO-, -NH-CO-CH2-, -NH-NH-,-NH-NH-CO-NH-, -NH-CO-NH-NH-, -CO-, -NH-SO2-NH-, -CO-NH-CO-NH-, -NH-CO-NH-CO-, -NH-CO-NH-SO2-, -NH-C(=NH)-NH-NH-, -NH-NH-C(=NH)-NH-, -CH=CH-, -CO-CH=CH-, -CH=CH-CO-, cyclopropan-1,2-di-yl, -NH-CH(COORC)-; R1 is selected from the group consisting of H, alkyl, -(CH2)p-A, wherein p = 0-4 and A = OH, -NRaRb, -COORc, -CONRaRb, -CONH(CH2)q-NRaRb, -CONH(CH2)q-COORc, wherein q = 1-4, Ra and Rb are H, alkyl, or Ra and Rb together with the nitrogen atom they are linked to form a 4-7 membered heterocyclic ring; Rc is H, alkyl or alkali or alkaline-earth metal; R is alkyl, cycloalkyl, arylalkyl, naphthyl, optionally substituted phenyl, aromatic or non aromatic 5 or 6 membered heterocyclic ring optionally benzofused; R2 is H or alkyl and the dotted line means an optional bond, for use as medicaments, in particular as antitumor agents.
• Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
  作者：Chunquan Sheng、Xiaoying Che、Wenya Wang、Shengzheng Wang、Yongbing Cao、Zhenyuan Miao、Jianzhong Yao、Wannian Zhang

  DOI：10.1016/j.ejmech.2011.03.019

  日期：2011.11

  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.
• Identification of 2,4,5-trisubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one-based small molecules as selective BRD9 binders
  作者：Ester Colarusso、Sara Ceccacci、Maria Chiara Monti、Erica Gazzillo、Assunta Giordano、Maria Giovanna Chini、Maria Grazia Ferraro、Marialuisa Piccolo、Dafne Ruggiero、Carlo Irace、Stefania Terracciano、Ines Bruno、Giuseppe Bifulco、Gianluigi Lauro

  DOI：10.1016/j.ejmech.2022.115018

  日期：2023.2

  approach for accelerating the selection of promising items and for driving the chemical synthesis of novel selective BRD9 binders. Moreover, the low molecular weight of the reported 2,4,5-trisubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one-based BRD9 binders suggests the possibility for further exploring the chemical space in order to obtain new analogues with improved potency.

  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