[4-(3-nitrophenyl)thiazol-2-yl]phenylamine | 325850-28-0

• 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: [4-(3-nitrophenyl)thiazol-2-yl]phenylamine
• 英文别名: 4-(3-nitrophenyl)-N-phenylthiazol-2-amine；4-(3-nitrophenyl)-N-phenyl-1,3-thiazol-2-amine
• CAS: 325850-28-0
• 化学式: C₁₅H₁₁N₃O₂S
• 分子量: 297.337
• InChiKey: ZCLYZPAJDYLLCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(3-nitrophenyl)thiazol-2-yl]phenylamine 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-bromo-N-(3-(2-(phenylamino)thiazol-4-yl)phenyl)benzenesulfonamide
  参考文献：
  名称：

  Structure activity relationship and optimization of N -(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells

  摘要：

  We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.054
• 作为产物：
  描述：

  间硝基苯乙酮 在 aluminum (III) chloride 、 溴 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 3.0h， 生成 [4-(3-nitrophenyl)thiazol-2-yl]phenylamine
  参考文献：
  名称：

  [EN] SUBSTITUTED HYDROPHOBIC BENZENE SULFONAMIDE THIAZOLE COMPOUNDS FOR USE IN TREATING CANCER
  [FR] COMPOSÉS DE THIAZOLE SULFONAMIDE DE BENZÈNE HYDROPHOBE SUBSTITUÉ UTILISABLES DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及通式（I）的化合物，其中R1可选自H、芳基和烷基，R2可选自H、烷基、芳基和CO-R6；R3可选自H、卤素、烷基、烯基、炔基、芳基、NHR7、NR7R8、OR7和SR7；R4可选自（C6-C12）烷基、（C2-C12）烯基、（C2-C12）炔基和（C6-C10）芳基，R5代表H、R6、芳基、OH、OR6、O-芳基、SH、SR6、S-芳基、CN、NO2、CF3、COOR6、SO2NR6R7、CONR6R7、NH2、NHR6、NH-芳基、NR6R7、NHCOR6或氨基酰基；R6是烷基，可选地取代卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或NH-二（烷基）；R7和R8相同或不同，是H或可选地取代卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或NH-二（烷基）的烷基，其药用可接受的盐和/或同分异构体、互变异构体、溶剂合物或同位素变体。这些化合物对治疗癌症有用。

  公开号：

  WO2017017004A1

文献信息

• 2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 2. Structure-Based Optimization and Investigation of Effects Specific to the Allosteric Mode of Action
  作者：Benoît Bestgen、Irina Kufareva、Weiguang Seetoh、Chris Abell、Rolf W. Hartmann、Ruben Abagyan、Marc Le Borgne、Odile Filhol、Claude Cochet、Thierry Lomberget、Matthias Engel

  DOI：10.1021/acs.jmedchem.8b01765

  日期：2019.2.28

  Protein CK2 has gained much interest as an anticancer drug target in the past decade. We had previously described the identification of a new allosteric site on the catalytic α-subunit, along with first small molecule ligands based on the 4-(4-phenylthiazol-2-ylamino)benzoic acid scaffold. In the present work, structure optimizations guided by a binding model led to the identification of the lead compound

  在过去的十年中，蛋白CK2作为抗癌药物已引起了广泛的关注。先前我们已经描述了催化α-亚基上新的变构位点的识别，以及基于4-（4-苯基噻唑-2-基氨基）苯甲酸支架的第一个小分子配体的鉴定。在目前的工作中，以结合模型为指导的结构优化导致了铅化合物2-羟基-4-（（4-（萘-2-基）噻唑-2-基）氨基）苯甲酸的鉴定（27） ，显示了对纯化的CK2α的亚微摩尔效价（IC50 = 0.6μM）。此外，与ATP竞争性候选药物CX-4945相比，27种诱导786-O肾细胞癌细胞的凋亡和细胞死亡（EC50 = 5μM）甚至更有效地抑制STAT3激活（EC50为1.6μM对5.3μM）。尤其，我们的变构配体抑制CK2的能力因各个底物而异。总之，新的变构口袋被证明是可药物治疗的部位，为开发有效和选择性的变构CK2抑制剂提供了绝佳的前景。
• Catalyst-free efficient synthesis of 2-aminothiazoles in water at ambient temperature
  作者：Taterao M. Potewar、Sachin A. Ingale、Kumar V. Srinivasan

  DOI：10.1016/j.tet.2008.03.082

  日期：2008.5

  A highly efficient and facile method has been described for the synthesis of substituted 2-aminothiazoles in water without any added catalyst or co-organic solvent. The reaction was carried out at ambient temperature and the products were obtained in excellent isolated yields. The developed protocol is successfully applied for the preparation of an anti-inflammatory drug, fanetizole.

  已经描述了一种在不添加任何催化剂或共有机溶剂的情况下在水中合成取代的2-氨基噻唑的高效且简便的方法。该反应在环境温度下进行，并且产物以优异的分离产率得到。所开发的方案已成功应用于抗炎药Fanetizole的制备。
• Effect of Substituents on the Regioselectivity of the Reaction of α-Tosyloxyketones with Thioureas in Acidic Medium: Access to 2-Aminothiazoles and 2-Imino-2,3-dihydrothiazoles
  作者：Ranjana Aggarwal、Rajiv Kumar、Dionisia Sanz、Rosa M. Claramunt

  DOI：10.1002/jhet.1676

  日期：2014.5

  Regioselective condensation of α‐tosyloxyacetophenones 1 and N‐substituted thioureas 2 in acidic medium to give regioisomers 2‐aminothiazoles I and 2‐imino‐2,3‐dihydrothiazoles II is largely influenced by the substituents present on 1 and 2. A mechanism, supported by DFT calculations has been proposed to explain the observed regioselectively.

  α-甲苯磺酰氧基苯乙酮1和N-取代的硫脲2在酸性介质中的区域选择性缩合反应产生区域异构体2-氨基噻唑I和2-亚氨基-2,3-二氢噻唑II在很大程度上受到1和2上存在的取代基的影响。已经提出了一种由DFT计算支持的机制来选择性地解释所观察到的区域。
• 2-Aminothiazole Derivatives as Selective Allosteric Modulators of the Protein Kinase CK2. 1. Identification of an Allosteric Binding Site
  作者：Benoît Bestgen、Isabelle Krimm、Irina Kufareva、Ahmed Ashraf Moustafa Kamal、Wei-Guang Seetoh、Chris Abell、Rolf W. Hartmann、Ruben Abagyan、Claude Cochet、Marc Le Borgne、Matthias Engel、Thierry Lomberget

  DOI：10.1021/acs.jmedchem.8b01766

  日期：2019.2.28

  studies, STD NMR, circular dichroism spectroscopy, and native mass spectrometry experiments demonstrated that the compounds bind in an allosteric pocket outside the ATP-binding site. Our data, combined with molecular docking studies, strongly suggested that this new binding site was located at the interface between the αC helix and the flexible glycine-rich loop. A first hit optimization led to compound 7

  CK2是一种普遍存在的Ser / Thr蛋白激酶，参与各种信号通路的控制，并且已知具有组成性活性。在本研究中，我们将芳基2-氨基噻唑确定为一类新的CK2抑制剂，它表现出非ATP竞争性作用方式，并稳定了溶液中CK2的非活性构象。酶动力学研究，STD NMR，圆二色光谱和天然质谱实验表明，这些化合物在ATP结合位点之外的变构口袋中结合。我们的数据与分子对接研究相结合，强烈暗示了这个新的结合位点位于αC螺旋与富柔性甘氨酸环之间的界面。首次命中优化导致化合物7的IC50为3。相对于纯化的CK2α为4μM，具有良好的选择性。因此，我们确定了一类针对变构口袋的新型CK2抑制剂，为进一步优化抗癌药物提供了巨大潜力。
• Substituted hydrophobic benzene sulfonamide thiazole compounds for use in treating cancer
  申请人：INSERM (Institut National de la Sante et de la Recherche Medicale)

  公开号：US10815207B2

  公开（公告）日：2020-10-27

  The present invention relates to compound of general formula (I) R1 is selected from H, aryl and alkyl, R2 is selected from H, alkyl, aryl and CO—R6; R3 is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR7, NR7R8, OR7 and SR7; R4 is selected from (C6-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl and (C6-C10) aryl, R5 represents H, R6, aryl, OH, OR6, O-aryl, SH, SR6, S-aryl, CN, NO2, CF3, COOR6, SO2NR6R7, CONR6R7, NH2, NHR6, NH-aryl, NR6R7, NHCOR6 or aminoacyl; R6 is alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R7 and R8 identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH2, O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.

  本发明涉及通式(I)的化合物 R1选自H、芳基和烷基，R2选自H、烷基、芳基和CO-R6；R3选自H、卤素、烷基、烯基、炔基、芳基、NHR7、NR7R8、OR7和SR7；R4 选自 (C6-C12)烷基、(C2-C12)烯基、(C2-C12)炔基和 (C6-C10)芳基，R5 代表 H、R6、芳基、OH、OR6、O-芳基、SH、SR6、S-芳基、CN、NO2、CF3、COOR6、SO2NR6R7、CONR6R7、NH2、NHR6、NH-芳基、NR6R7、NHCOR6 或氨基酰基；R6 是任选被卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或 NH-二（烷基）取代的烷基；R7 和 R8 相同或不同，是 H 或任选被卤素、OH、SH、NH2、O-烷基、S-烷基、NH-烷基或 NH-二（烷基）取代的烷基、它们的药学上可接受的盐和/或其异构体、同分异构体、溶解物或同位素变体。这些化合物可用于治疗癌症。