4-amino-5-acetyl-2-(4-morpholinyl)-thiazole | 1044860-88-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-amino-5-acetyl-2-(4-morpholinyl)-thiazole
• 英文别名: 1-(4-amino-2-morpholinothiazol-5-yl)ethanone；5-acetyl-4-amino-2-(4-morpholinyl)-1,3-thiazole；1-(4-Amino-2-morpholin-4-yl-1,3-thiazol-5-yl)ethanone；1-(4-amino-2-morpholin-4-yl-1,3-thiazol-5-yl)ethanone
• CAS: 1044860-88-9
• 化学式: C₉H₁₃N₃O₂S
• 分子量: 227.287
• InChiKey: QQYMLVWFTCORFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-amino-5-acetyl-2-(4-morpholinyl)-thiazole 在 亚硝酸特丁酯 、 copper(ll) bromide 作用下， 以 乙腈 为溶剂， 以55%的产率得到1-(4-bromo-2-morpholino-1,3-thiazol-5-yl)ethanone
  参考文献：
  名称：

  4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells

  摘要：

  The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed similar to 10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na+/K+-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.046
• 作为产物：
  描述：

  在 potassium carbonate 作用下， 反应 1.0h， 生成 4-amino-5-acetyl-2-(4-morpholinyl)-thiazole
  参考文献：
  名称：

  4-氨基-5-肉桂基噻唑类化合物的合成及生物学评价

  摘要：

  设计并合成了一系列4-氨基-5-肉桂基噻唑3a-p，它们是类查尔酮样的抗癌药。评价了合成的衍生物3a-p对三种不同的人类癌细胞系包括MCF-7，HepG2和SW480的体外抗增殖活性。大多数化合物可以显着阻止受试细胞系的增殖。尤其是，吡咯烷衍生物3e，即（E）-1-（4-氨基-2-（吡咯烷-1-基）噻唑-5-基）-3-（2，4-二氯苯基）丙-2-烯- 1-one显示出有希望的活性，尤其是针对HepG2细胞（IC 50  = 10.6μg/ ml）。流式细胞仪分析表明原型化合物3e 通过阻断G2期的细胞周期并诱导凋亡，可以阻止HepG2细胞的增殖。

  DOI：

  10.1016/j.ejmech.2018.01.015

文献信息

• One-pot synthesis of new 2,4,5-trisubstituted 1,3-thiazoles and 1,3-selenazoles
  作者：David Thomae、Enrico Perspicace、Zhanjie Xu、Dorothée Henryon、Serge Schneider、Stéphanie Hesse、Gilbert Kirsch、Pierre Seck

  DOI：10.1016/j.tet.2009.01.104

  日期：2009.4

  In this work, we describe the synthesis of new 2,4,5-trisubstituted-1,3-thiazoles and 1,3-selenazole achieved by an easy one-pot four-step procedure. Expected compounds were obtained in good yield from dimethyl cyanodithioimidocarbonate, which was the common starting material for the preparation of all 1,3-thiazoles and 1,3-selenazoles. Chemical diversity was introduced on thiazole and selenazole rings

  在这项工作中，我们描述了通过简单的一锅四步法实现的新2,4,5-三取代-1,3-噻唑和1,3-硒唑的合成。从氰基二硫代亚氨基碳酸二甲酯中可以以高收率获得预期的化合物，后者是制备所有1,3-噻唑和1,3-硒唑的常用原料。通过改变所用的胺和活化的卤化物，在噻唑和硒唑环上引入了化学多样性。
• Heterocondensed thiophenes and thiazoles by THORPE-ZIEGLER cyclization
  作者：Margit Gruner、Gesine Böttcher、Karl Gewald

  DOI：10.1002/jhet.5570450419

  日期：2008.7

  The syntheses of novel thieno-pyridones, thiazolo-pyridones, thiazolo-pyridines and amino- and diamino-dieno-pyridines were described. Simultaneously, it was demonstrated that in these compounds and in the related 3-aminothiophenes the replacement of the methylthio by the morpholino group is possible. The structures were characterized using 1H-, 13C-NMR, IR and elemental analysis.

  描述了新颖的噻吩并吡啶酮，噻唑并吡啶酮，噻唑并吡啶以及氨基和二氨基二酮基吡啶的合成。同时证明，在这些化合物和相关的3-氨基噻吩中，可以用吗啉代基团代替甲硫基。使用1 H-，13 C-NMR，IR和元素分析对结构进行表征。
• 4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells
  作者：Florence Lefranc、Zhanjie Xu、Patricia Burth、Véronique Mathieu、Germain Revelant、Mauro Velho de Castro Faria、Caroline Noyon、Diogo Gomes Garcia、Damien Dufour、Céline Bruyère、Cassiano Felippe Gonçalves-de-Albuquerque、Pierre Van Antwerpen、Bernard Rogister、Stéphanie Hesse、Gilbert Kirsch、Robert Kiss

  DOI：10.1016/j.ejmech.2013.01.046

  日期：2013.5

  The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed similar to 10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na+/K+-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of 4-amino-5-cinnamoylthiazoles as chalcone-like anticancer agents
  作者：Adileh Ayati、Rezvan Esmaeili、Setareh Moghimi、Tayebeh Oghabi Bakhshaiesh、Zahra Eslami-S、Keivan Majidzadeh-A、Maliheh Safavi、Saeed Emami、Alireza Foroumadi

  DOI：10.1016/j.ejmech.2018.01.015

  日期：2018.2

  A series of 4-amino-5-cinnamoylthiazoles 3a-p were designed and synthesized as chalcone-like anticancer agents. The synthesized derivatives 3a-p were evaluated for their in vitro antiproliferative activities against three different human cancer cell lines including MCF-7, HepG2 and SW480. Most of compounds could significantly prevent proliferation of tested cell lines. In particular, the pyrrolidine

  设计并合成了一系列4-氨基-5-肉桂基噻唑3a-p，它们是类查尔酮样的抗癌药。评价了合成的衍生物3a-p对三种不同的人类癌细胞系包括MCF-7，HepG2和SW480的体外抗增殖活性。大多数化合物可以显着阻止受试细胞系的增殖。尤其是，吡咯烷衍生物3e，即（E）-1-（4-氨基-2-（吡咯烷-1-基）噻唑-5-基）-3-（2，4-二氯苯基）丙-2-烯- 1-one显示出有希望的活性，尤其是针对HepG2细胞（IC 50  = 10.6μg/ ml）。流式细胞仪分析表明原型化合物3e 通过阻断G2期的细胞周期并诱导凋亡，可以阻止HepG2细胞的增殖。