N-(2,4-difluorophenyl)hydrazinecarboxamide | 777826-82-1

• 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: N-(2,4-difluorophenyl)hydrazinecarboxamide
• 英文别名: 1-Amino-3-(2,4-difluorophenyl)urea
• CAS: 777826-82-1
• 化学式: C₇H₇F₂N₃O
• 分子量: 187.149
• InChiKey: YHIZHTAPHOOODV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 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：
  4

反应信息

• 作为反应物：
  描述：

  N-(2,4-difluorophenyl)hydrazinecarboxamide 在 potassium carbonate 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 N-(2,4-difluorophenyl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide
  参考文献：
  名称：

  Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: Synthesis and neuropharmacology

  摘要：

  We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-alpha), nitric oxide and cannabinoid receptor subtype 1 (CBI). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tertbutyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED50 = 23.8 mg/kg) and partial sciatic nerve injury (ED50 = 29.0 mg/kg) models with CB receptor activity (IC50 = 49.6 nM) and inhibitory effect on TNF-alpha (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.022

文献信息

• Identification of 1,3-thiazinan-4-one urea-based derivatives as potent FLT3/VEGFR2 dual inhibitors for the treatment of acute myeloid leukemia
  作者：Xingwei Xu、Liping Hu、Mengmeng Fan、Ziwei Hu、Qiming Li、Huan He、Baohui Qi

  DOI：10.1016/j.molstruc.2021.131862

  日期：2022.2

  synthesized, and structure-activity relationships (SARs) analysis based on the biological evaluation and docking study led to the discovery of several more potent FLT3/VEGFR2 dual inhibitors. Among them, 1-(2-(3-fluoro-4-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinolin-4-yl)oxy)phenyl)-4-oxo-1,3-thiazinan-3-yl)-3-phenylurea (4f) possessed significantly inhibitory activities against FLT3, VEGFR2

  阻断多种癌蛋白或通路是目前癌症治疗中更有效的方法。在这项研究中，对先导化合物N 1 -(2,4-二氟苯基)- N 3 -(2-(3-fluoro-4-((6-甲氧基-7-(3-(4 -甲基哌嗪-1-基)丙氧基)喹啉-4-基)氧基)苯基)-4-氧噻唑啉-3-基)脲 ( BMC-17b)，这是在我们之前的研究中获得的，并显示出对 FLT3 和 VEGFR2 的有效抑制活性。合成了九种新型衍生物，基于生物学评价和对接研究的构效关系 (SAR) 分析导致发现了几种更有效的 FLT3/VEGFR2 双抑制剂。其中，1-(2-(3-氟-4-((6-甲氧基-7-(3-(4-甲基哌嗪-1-基)丙氧基)喹啉-4-基)氧基)苯基)-4- oxo-1,3-thiazinan-3-yl)-3-phenylurea ( 4f ) 对 FLT3、VEGFR2 和 FLT3 驱动的 AML MV4-11 细胞具有显着的抑制活性，IC
• Synthesis of 3-(tri/difluoromethyl)-1<i>H</i>-1,2,4-triazol-5(4<i>H</i>)-ones <i>via</i> the cyclization of hydrazinecarboxamides with tri/difluoroacetic anhydride
  作者：Yi You、Yueji Chen、Chenhui You、Junwen Wang、Zhiqiang Weng

  DOI：10.1039/c9ob01865d

  日期：——

  An efficient method for the synthesis of structurally diverse 4-aryl-3-(tri/difluoromethyl)-1H-1,2,4-triazol-5(4H)-ones through the cyclization of hydrazinecarboxamides with tri/difluoroacetic anhydride is presented. The method is simple and environmentally benign, providing tri/difluoromethylated 1,2,4-triazol-5(4H)-ones in moderate-to-good yields. A mechanism is proposed to proceed via a tandem reaction

  提出了一种通过肼羧酰胺与三/二氟乙酸酐环化合成结构多样的4-芳基-3-（三/二氟甲基）-1H-1,2,4-三唑-5（4H）-的有效方法。该方法简单且对环境无害，可以以中等至良好的产率提供三/二氟甲基化的1,2,4-三唑-5（4H）-一。提出了通过三/二氟乙酰化，亲核加成和水消除的串联反应进行的机制。这些化合物中的一些表现出有希望的杀虫活性。
• Dérivés d'indane-1,3-dione et d'indane-1,2,3-trione, leurs procédés de préparation et leur application en thérapeutique
  申请人：INNOTHERA

  公开号：EP0566445A1

  公开（公告）日：1993-10-20

  Composés utiles en thérapeutique de formule : dans laquelle R₂ et R₃ représentent indépendamment l'un de l'autre H, alkoxy en C₁-C₄ ou OH et (A, B) = (oxygène, oxygène) auquel cas l'un parmi R et R₁ représente OH, halogène, amino secondaire ou amine tertiaire et l'autre représente NHNHCONHR₄ ou bien R et R₁ forment ensemble =N-NH-CX-NHR₅, =N-NH-CX-N(phényle)₂, =N-NH-CX-NH-NH-R₅, =N-NH-C(SCH₃)=N-R₆ ou =N-N=C(SCH₃)-NH-R₆ ; ou (A, B) = (N-OH, oxygène) auquel cas R et R₁ forment ensemble =N-NH-CX-NHR₅ ou =N-NH-CX-N(phényle)₂ ; ou (A, B) = (N-NH-CX-NHR₅, oxygène) auquel cas R et R₁ forment ensemble =N-NH-CX-NHR₅ ; ou (A, B) = (N-OH, N-OH) auquel cas R et R₁ forment ensemble =N-NH-CX-NHR₅ ou =N-NH-CX-N(phényle)₂.

  可用于配方治疗的化合物 ： 其中 R₂ 和 R₃ 各自独立地代表 H、C₁-C₄ 烷氧基或 OH 以及 (A, B) = (氧, 氧)，在这种情况下，R 和 R₁ 中的一个代表 OH、卤素、或 R 和 R₁ 共同形成 =N-NH-CX-NHR₅、=N-NH-CX-N(苯基)₂、=N-NH-CX-NH-NH-R₅、=N-NH-C(SCH₃)=N-R₆ 或 =N-N=C(SCH₃)-NH-R₆ ；或 (A，B) = (N-OH，氧)，在这种情况下，R 和 R₁ 共同形成 =N-NH-CX-NHR₅ 或 =N-NH-CX-N (苯基)₂；或（A，B）＝（N-NH-CX-NHR₅，氧），在这种情况下，R 和 R₁ 共同形成＝N-NH-CX-NHR₅；或（A，B）＝（N-OH，N-OH），在这种情况下，R 和 R₁ 共同形成＝N-NH-CX-NHR₅或＝N-NH-CX-N（苯基）₂。
• Identification of novel N-(2-aryl-1, 3-thiazolidin-4-one)-N-aryl ureas showing potent multi-tyrosine kinase inhibitory activities
  作者：Baohui Qi、Ying Yang、Huan He、Xupeng Yue、Yuting Zhou、Xing Zhou、Yuying Chen、Min Liu、Anmian Zhang、Fachang Wei

  DOI：10.1016/j.ejmech.2018.01.061

  日期：2018.2

  A total of 29 novel compounds bearing N-1-(2-aryl-1, 3-thiazolidin-4-one)-N-3-aryl ureas were designed, synthesized and evaluated for their biological activities. The structure-activity relationships (SARs) and binding modes of this series of compounds were clarified together. Compound 29b was identified possessing high potency against multi-tyrosine kinases including Ron, c-Met, c-Kit, KDR, Src and IGF-1R, etc. In vitro antiproliferation and cytotoxicity of compound 29b against A549 cancer cell line were confirmed by IncuCyte live-cell imaging. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Discovery of thiazolidin-4-one urea analogues as novel multikinase inhibitors that potently inhibit FLT3 and VEGFR2
  作者：Baohui Qi、Xingwei Xu、Ying Yang、Yuting Zhou、Tao Chen、Guowei Gong、Xupeng Yue、Xin Xu、Liping Hu、Huan He

  DOI：10.1016/j.bmc.2019.03.049

  日期：2019.5

  A series of novel thiazolidine-4-one urea analogues were designed, synthesized and biologically evaluated. The structure-activity relationship (SAR) at several positions of the scaffolds was investigated and its binding mode was analyzed by molecular modeling studies. Compound 17b proved to be the most potent one, and IC50 values against A549 and HT-29 cancer cell lines were 0.65 mu M and 0.11 mu M, respectively. The results of kinase profile demonstrated that compound 17b is a multikinase inhibitor that potently inhibits FLT3 (IC50 = 8.6 nM) and VEGFR2 (IC50 = 18.7 nM). The results of real-time live-cell imaging indicated that compound 17b showed excellent cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, which was significantly potent than that of Cabozantinib. In addition, in vitro antitumor activity was associated with inducing cancer cell apoptosis and suppression of cancer cell migration.