1-(3-aminophenyl)-3-(3-chloro-4-fluorophenyl)urea | 721449-39-4

• 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-(3-aminophenyl)-3-(3-chloro-4-fluorophenyl)urea
• CAS: 721449-39-4
• 化学式: C₁₃H₁₁ClFN₃O
• 分子量: 279.701
• InChiKey: FFSYHCXOFBEEOL-UHFFFAOYSA-N

物化性质

• 沸点：
  346.7±42.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 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-(3-aminophenyl)-3-(3-chloro-4-fluorophenyl)urea 在 盐酸 、 potassium iodide 作用下， 以 N-甲基吡咯烷酮 、 异丙醇 为溶剂， 反应 35.0h， 生成 1-(3-chloro-4-fluorophenyl)-3-(3-(7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-ylamino)phenyl)urea
  参考文献：
  名称：

  Design and discovery of 4-anilinoquinazoline ureas as multikinase inhibitors targeting BRAF, VEGFR-2 and EGFR

  摘要：

  4-苯胺基喹唑啉脲是根据混合设计方法设想的，该方法基于激酶药物发现中的两个特权药效团，即4-苯胺基喹唑啉和不对称二芳基脲。在我们的构效关系 (SAR) 活动中，合成了标题化合物，并通过生化分析对其激酶抑制活性进行了分析。标题化合物 18-20 被发现是多激酶抑制剂，对 BRAF、BRAF V600E、VEGFR-2 和 EGFR 具有显着活性。 BRAF 和 VEGFR-2 的 DFG-out 构象的分子对接表明它们可能是 II 型抑制剂。

  DOI：

  10.1039/c3md00096f
• 作为产物：
  描述：

  tert-butyl N-[3-[(3-chloro-4-fluorophenyl)carbamoylamino]phenyl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 17.0h， 以100%的产率得到1-(3-aminophenyl)-3-(3-chloro-4-fluorophenyl)urea
  参考文献：
  名称：

  [DE] VERFAHREN ZUR INHIBIERUNG DER REPLIKATION VON HERPESVIREN
  [EN] METHOD FOR INHIBITING THE REPLICATION OF HERPES VIRUSES
  [FR] PROCEDE POUR INHIBER LA REPLICATION DE VIRUS HERPETIQUES

  摘要：

  公开号：

  WO2004060860A3

文献信息

• Method for inhibiting the replication of herpes viruses
  申请人：Betz Ulrich

  公开号：US20070004735A1

  公开（公告）日：2007-01-04

  The invention relates to a method for inhibiting the replication of herpesviruses, to methods for identifying compounds which inhibit the replication of herpesviruses using this method, to compounds having activity against herpesviruses, to methods for their preparation and to their use for producing medicaments for the treatment of herpes infections.

  本发明涉及一种抑制疱疹病毒复制的方法，使用该方法鉴定抑制疱疹病毒复制的化合物的方法，具有抗疱疹病毒活性的化合物，其制备方法以及用于制备治疗疱疹感染药物的方法。
• Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization
  作者：Ling-Ling Yang、Guo-Bo Li、Heng-Xiu Yan、Qi-Zheng Sun、Shuang Ma、Pan Ji、Ze-Rong Wang、Shan Feng、Jun Zou、Sheng-Yong Yang

  DOI：10.1016/j.ejmech.2012.08.007

  日期：2012.10

  Aberrant activation of casein kinase 1 (CK1) has been demonstrated to be implicated in the pathogenesis of cancer and various central nervous system disorders. Discovery of CK1 inhibitors has thus attracted much attention in recent years. In this account, we describe the discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors. An optimal common-feature pharmacophore hypothesis, termed Hypo2, was firstly generated, followed by virtual screening using Hypo2 against several chemical databases. One of the best hit compounds, N6-(4-chlorophenyl)-1H-pyrazolo [3,4-d]pyrimidine-3,6-diamine, was chosen for the subsequent hit-to-lead optimization under the guide of Hypo2, which led to the discovery of a new lead compound (1-(3-(3-amino-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)phenyl)-3-(3-chloro-4-fluorophenyl)urea) that potently inhibits CK1 with an IC50 value of 78 nM. (c) 2012 Elsevier Masson SAS. All rights reserved.
• 4-POSITION SUBSTITUTED PYRAZOLOPYRIMIDINE DERIVATIVE, AND USE THEREOF IN DRUG PREPARATION
  申请人：GUANGXI WUZHOU PHARMACEUTICALS (GROUP) CO., LTD.

  公开号：EP2889298B1

  公开（公告）日：2018-05-02
• [DE] VERFAHREN ZUR INHIBIERUNG DER REPLIKATION VON HERPESVIREN<br/>[EN] METHOD FOR INHIBITING THE REPLICATION OF HERPES VIRUSES<br/>[FR] PROCEDE POUR INHIBER LA REPLICATION DE VIRUS HERPETIQUES
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004060860A3

  公开（公告）日：2005-02-10
• Design and discovery of 4-anilinoquinazoline ureas as multikinase inhibitors targeting BRAF, VEGFR-2 and EGFR
  作者：Qingwen Zhang、Yuanyuan Diao、Fei Wang、Ying Fu、Fei Tang、Qidong You、Houyuan Zhou

  DOI：10.1039/c3md00096f

  日期：——

  4-Anilinoquinazoline ureas were envisaged according to the hybrid-design approach based upon two privileged pharmacophores in kinase drug discovery, i.e. 4-anilinoquinazoline and unsymmetrical diaryl urea. In our structure–activity relationships (SAR) campaign, title compounds were synthesized and profiled in biochemical assay for their kinase inhibitory activity. Title compounds 18–20 were found to be multikinase inhibitors with profound activity against BRAF, BRAF V600E, VEGFR-2 and EGFR. Molecular docking into DFG-out conformations of BRAF and VEGFR-2 suggested that they might be type II inhibitors.

  4-苯胺基喹唑啉脲是根据混合设计方法设想的，该方法基于激酶药物发现中的两个特权药效团，即4-苯胺基喹唑啉和不对称二芳基脲。在我们的构效关系 (SAR) 活动中，合成了标题化合物，并通过生化分析对其激酶抑制活性进行了分析。标题化合物 18-20 被发现是多激酶抑制剂，对 BRAF、BRAF V600E、VEGFR-2 和 EGFR 具有显着活性。 BRAF 和 VEGFR-2 的 DFG-out 构象的分子对接表明它们可能是 II 型抑制剂。