5-phenethyl-thiazol-2-ylamine | 100988-28-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-phenethyl-thiazol-2-ylamine
• 英文别名: 5-phenethyl-2-thiazolamine；5-(2-phenylethyl)-2-Thiazolamine；5-(2-phenylethyl)-1,3-thiazol-2-amine
• CAS: 100988-28-1
• 化学式: C₁₁H₁₂N₂S
• 分子量: 204.296
• InChiKey: FFDIQZFHXKHMES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-环己基丙酰氯 、 5-phenethyl-thiazol-2-ylamine 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以79%的产率得到N-(5-phenethylthiazol-2-yl)-3-cyclohexanepropanamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

  摘要：

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.006
• 作为产物：
  描述：

  4-苯基丁醛 在 N-氯代丁二酰亚胺 、 L-脯氨酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 5-phenethyl-thiazol-2-ylamine
  参考文献：
  名称：

  [EN] AUTOTAXIN INHIBITORS
  [FR] INHIBITEURS DE L'AUTOTAXINE

  摘要：

  本发明涉及如下式（I）的化合物：其中R1、R2、R3、R4a、R4b、R4C、R4d、L、A、Q、W和HET分别如本文所定义。本发明的化合物是自体脂肪酶（ATX）酶活性的抑制剂。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及ATX活性有所涉及的其他疾病或情况（如纤维化）中的用途。

  公开号：

  WO2016124938A1

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：MISSION THERAPEUTICS LTD

  公开号：WO2016046530A1

  公开（公告）日：2016-03-31

  The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.

  本发明涉及新型化合物和制备去泛素化酶（DUBs）抑制剂的方法。具体而言，本发明涉及抑制泛素C端水解酶L1（UCHL1）。本发明进一步涉及在癌症和其他适应症治疗中使用DUB抑制剂。本发明的化合物包括具有式（I）或其药用可接受盐的化合物，其中R1至R8如本文所定义。
• Discovery of 2-Aminothiazole Derivatives as Antitumor Agents
  作者：Minghua Li、Yoo-Jin Sim、Seung-Wook Ham

  DOI：10.5012/bkcs.2010.31.6.1463

  日期：2010.6.20

  2-4 In the course of searching for anticancer agents, 2-aminothiazole derivatives were recently prepared by varying the 2-amino position and the 5-substituted group of the 2-aminothiazole core in a high-speed parallel format using the procedure that was described in the literature. 5 The variations in the 5-position of the 2-amino-1,3-thiazole core were carried out though the condensation of thiourea

  2-4 在寻找抗癌剂的过程中，最近通过改变 2-氨基噻唑核心的 2-氨基位置和 5-取代基团以高速平行形式使用以下方法制备了 2-氨基噻唑衍生物：文献中描述的。5 2-氨基-1,3-噻唑核的 5 位变化是通过硫脲和氯醛的缩合来进行的，它们是市售的或在脯氨酸催化剂存在下使用 NCS 获得的。6
• Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity
  作者：Yong-Hak Kim、Siyoung Ha、Jungwon Kim、Seung Wook Ham

  DOI：10.1002/cmdc.201600159

  日期：2016.7.5

  We found that aminothiazole derivative (E)‐N‐(5‐benzylthiazol‐2‐yl)‐3‐(furan‐2‐yl)acrylamide (1) has strong anticancer activity, and undertook proteomics approaches to identify the target protein of compound 1, importin β1 (KPNB1). A competitive binding assay using fluorescein‐labeled 1 showed that 1 has strong binding affinity for KPNB1 (Kd: ∼20 nm). Furthermore, through western blotting assays for

  我们发现氨基噻唑衍生物（E）-N-（5-苄基噻唑-2-基）-3-（呋喃-2-基）丙烯酰胺（1）具有很强的抗癌活性，并采取了蛋白质组学方法来鉴定化合物的目标蛋白1，输入蛋白β1（KPNB1）。使用荧光素标记的1进行的竞争性结合测定表明1具有对KPNB1的强结合亲和力（K d：〜20 n m）。此外，通过针对KPNB1，KPNA2，EGFR，ErbB2和STAT3的蛋白质印迹分析，我们确认了1对importin途径具有抑制作用。KPBN1似乎在几种癌细胞中过表达，并且siRNA诱导的KPNB1抑制作用显示出对癌细胞增殖的显着抑制作用，而使非癌细胞没有受到影响。因此，化合物1是开发KPNB1靶向抗癌药的有希望的新线索。荧光素标记的1可能是开发新型KPNB1抑制剂的有用定量探针。
• Modulators of ATP-Binding Cassette transporters
  申请人：Ruah Sarah Hadida

  公开号：US20080176899A1

  公开（公告）日：2008-07-24

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节因子（“CFTR”），以及其组成物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
  申请人：Hadida-Ruah Sara Sabina

  公开号：US20110306637A1

  公开（公告）日：2011-12-15

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节因子（“CFTR”），以及其组合物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。