2-amino-5-(p-aminophenyl)-4-methylthiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-amino-5-(p-aminophenyl)-4-methylthiazole
• 英文别名: 5-(4-aminophenyl)-4-methylthiazol-2-amine；5-(4-amino-phenyl)-4-methyl-thiazol-2-ylamine；5-(4-Aminophenyl)-4-methyl-1,3-thiazol-2-amine；5-(4-aminophenyl)-4-methyl-1,3-thiazol-2-amine
• 化学式: C₁₀H₁₁N₃S
• 分子量: 205.283
• InChiKey: BEAUMUVRUVYYNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-5-(p-aminophenyl)-4-methylthiazole 在 盐酸 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 二甲基亚砜 、 乙腈 为溶剂， 反应 1.0h， 生成 N-[5-(4-aminophenyl)-4-methyl-1,3-thiazol-2-yl]-2-[(4R)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]acetamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel aminothiazoles as antiviral compounds acting against human rhinovirus

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.04.077
• 作为产物：
  描述：

  苯胺基硫脲 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 生成 2-amino-5-(p-aminophenyl)-4-methylthiazole
  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

• Abolishing Dopamine D_2long/D₃ Receptor Affinity of Subtype-Selective Carbamoylguanidine-Type Histamine H₂ Receptor Agonists
  作者：Katharina Tropmann、Merlin Bresinsky、Lisa Forster、Denise Mönnich、Armin Buschauer、Hans-Joachim Wittmann、Harald Hübner、Peter Gmeiner、Steffen Pockes、Andrea Strasser

  DOI：10.1021/acs.jmedchem.1c00692

  日期：2021.6.24
• 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.
• Bose, Journal of the Indian Chemical Society, 1927, vol. 4, p. 334
  作者：Bose

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  日期：——
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  作者：Beyer、Bulka

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• Bose; Sen, Journal of the Indian Chemical Society, 1928, vol. 5, p. 653
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