5-(4-aminophenyl)-1,3-thiazol-2-amine | 90349-87-4

• 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: 5-(4-aminophenyl)-1,3-thiazol-2-amine
• 英文别名: 5-(4-aminophenyl)-2-amino-1,3-thiazole；2-Amino-5-p-aminophenylthiazole；5-(4-amino-phenyl)-thiazol-2-ylamine；5-(p-Aminophenyl)-2-thiazolamine
• CAS: 90349-87-4
• 化学式: C₉H₉N₃S
• 分子量: 191.257
• InChiKey: CGEBKMQTSUAAMN-UHFFFAOYSA-N

物化性质

• 熔点：
  197 °C
• 沸点：
  417.1±20.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储温度应保持在2-8°C，并请避免光线直射。

反应信息

• 作为反应物：
  描述：

  5-(4-aminophenyl)-1,3-thiazol-2-amine 在 吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 8.0h， 生成 C₃₁H₃₆N₈O₃S
  参考文献：
  名称：

  Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations

  摘要：

  Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives as highly potent and selective FLT3 inhibitors with good in vivo efficacy using an intravenous (IV) route. However, the poor bioavailability of these pyrazole compounds limits the development of these promising antileukemic compounds for clinical use. Herein, we describe a novel class of 5-phenyl-thiazol-2-ylamine compounds that are multi-targeted FLT3 inhibitors. From this class of compounds, compound 7h was very potent against AML cell lines and exhibited excellent oral efficacy in AML xenograft models. In addition, further studies demonstrated that compound 7h exhibited potent in vitro and in vivo activities against clinically relevant AC220 (3)-resistant kinase domain mutants of FLT3-ITD. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.05.008
• 作为产物：
  描述：

  苯胺基硫脲 在 盐酸 作用下， 以 水 为溶剂， 反应 15.0h， 生成 5-(4-aminophenyl)-1,3-thiazol-2-amine
  参考文献：
  名称：

  [5,5] Sigmatropic shift of N-phenyl-N′-(2-thiazolyl)hydrazines and N,N′-bis(2-thiazolyl)hydrazines into 2-amino-5-(p-aminophenyl)thiazoles and 5,5′-bis(2-aminothiazole) derivatives

  摘要：

  [5,5] Sigmatropic shift of N-phenyl-N'-(2-thiazolyl)hydrazines and N,N'-bis(2-thiazolyl)hydrazines in acid-catalyzed benzidine-type rearrangement into 2-amino-5-(p-aminophenyl)thiazoles and 5,5'-bis(2-aminothiazole) derivatives is described, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)00493-7

文献信息

• PYRAZOLE COMPOUNDS AND THIAZOLE COMPOUNDS AS PROTEIN KINASES INHIBITORS
  申请人：Jiaang Weir-Torn

  公开号：US20120225880A1

  公开（公告）日：2012-09-06

  A compound of formula (I): wherein A, B, D, X, Y, R 1 , R 2 , R 3 , m, p, and q are defined herein. Also disclosed is a method for inhibiting FMS-like tyrosine kinase 3, aurora kinase, or vascular endothelial growth factor receptor.

  其中A、B、D、X、Y、R1、R2、R3、m、p和q的化合物的化学式（I）： 还公开了一种抑制FMS样酪氨酸激酶3、极光激酶或血管内皮生长因子受体的方法。
• Design, Synthesis, and Anticancer Activity of New Derivatives of Thiazole and Imidazole
  作者：I. M. El-Deen、E. H. Elsayed、M. El-Ahwany、M. S. Abd El-Azez

  DOI：10.1134/s1070363220120191

  日期：2020.12

  Abstract A number of nitrogen heterocyclic derivatives, namely 1,3-thiazole and imidazolidine-2-thione, have been synthesized and their structures confirmed by IR, 1H and 13C NMR, and mass spectra. Cytotoxic activity of some synthesized products has been tested against human hepatocellular carcinoma (HepG2) cell line using the MTT assay. The most potent anti-proliferative agent demonstrates activity

  摘要 已经合成了许多氮杂环衍生物，即1，3-噻唑和咪唑烷-2-硫酮，并通过IR，1 H和13 C NMR以及质谱证实了它们的结构。已使用MTT分析法测试了某些合成产物对人肝细胞癌（HepG2）细胞的细胞毒活性。最有效的抗增殖剂显示出比参考化合物阿霉素高2倍的活性。三种化合物的特征在于其针对VEGFR-2的IC 50值。化合物6的细胞周期分析表明，细胞周期停滞在G1期，细胞积累在G1前期，表明细胞毒性活性是通过凋亡途径进行的。
• Über die Eigenschaften einiger Phenyl-azol-Derivate
  作者：J. Eckenstein、E. Brogle、E. Sorkin、H. Erlenmeyer

  DOI：10.1002/hlca.19500330535

  日期：——

  Es wird über die Synthesen einiger Phenyl-azol-Derivate berichtet, von denen auf Grund der Struktur eine tuberkulostatische Aktivität zu erwarten war.

  报道了一些苯基-唑衍生物的合成，基于它们的结构，预期从中可以得到抑菌活性。
• Design, synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus
  作者：Anne Décor、Chantal Grand-Maître、Oliver Hucke、Jeff O’Meara、Cyrille Kuhn、Léa Constantineau -Forget、Christian Brochu、Eric Malenfant、Mégan Bertrand-Laperle、Josée Bordeleau、Elise Ghiro、Marc Pesant、Gulrez Fazal、Vida Gorys、Michael Little、Colette Boucher、Sylvain Bordeleau、Pascal Turcotte、Tim Guo、Michel Garneau、Catherine Spickler、Annick Gauthier

  DOI：10.1016/j.bmcl.2013.04.077

  日期：2013.7

  We describe here the design, synthesis and biological evaluation of antiviral compounds acting against human rhinovirus (HRV). A series of aminothiazoles demonstrated pan-activity against the HRV genotypes screened and productive structure-activity relationships. A comprehensive investigational library was designed and performed allowing the identification of potent compounds with lower molecular weight and improved ADME profile. 31d-1, 31d-2, 31f showed good exposures in CD-1 mice. The mechanism of action was discovered to be a host target: the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII beta). The identification of the pan-HRV active compound 31f combined with a structurally distinct literature compound T-00127-HEV1 allowed the assessment of target related tolerability of inhibiting this kinase for a short period of time in order to prevent HRV replication. (c) 2013 Elsevier Ltd. All rights reserved.
• Discovery of Conformational Control Inhibitors Switching off the Activated c-KIT and Targeting a Broad Range of Clinically Relevant c-KIT Mutants
  作者：Tsung-Sheng Wu、Wen-Hsing Lin、Hui-Jen Tsai、Ching-Cheng Hsueh、Tsu Hsu、Pei-Chen Wang、Hui-You Lin、Yi-Hui Peng、Cheng-Tai Lu、Lung-Chun Lee、Chih-Hsiang Tu、Fang-Chun Kung、Hui-Yi Shiao、Teng-Kuang Yeh、Jen-Shin Song、Jia-Yu Chang、Yu-Chieh Su、Li-Tzong Chen、Chiung-Tong Chen、Weir-Torn Jiaang、Su-Ying Wu

  DOI：10.1021/acs.jmedchem.8b01845

  日期：2019.4.25

  Drug resistance due to acquired mutations that constitutively activate c-KIT is a significant challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). Herein, we identified 1-(5-ethyl-isoxazol-3-yl)-3-(4-2-[6-(4-ethylpiperazin-1-yl)pyrimidin-4-ylamino]-thiazol-5-yl}phenyl)urea (10a) as a potent inhibitor against unactivated and activated c-KIT. The binding of 10a induced rearrangements of the DFG motif, alpha C-helix, juxtamembrane domain, and the activation loop to switch the activated c-KIT back to its structurally inactive state. To the best of our knowledge, it is the first structural evidence demonstrating how a compound can inhibit the activated c-KIT by switching back to its inactive state through a sequence of conformational changes. Moreover, 10a can effectively inhibit various c-KIT mutants and the proliferation of several GIST cell lines. The distinct binding features and superior inhibitory potency of 10a, together with its excellent efficacy in the xenograft model, establish 10a as worthy of further clinical evaluation in the advanced GISTs.

表征谱图