(4-amino-2-(methylthio)thiazol-5-yl)(3,4,5- trimethoxyphenyl)methanone | 1347690-25-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-amino-2-(methylthio)thiazol-5-yl)(3,4,5- trimethoxyphenyl)methanone
• 英文别名: (4-Amino-2-methylsulfanyl-1,3-thiazol-5-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1347690-25-8
• 化学式: C₁₄H₁₆N₂O₄S₂
• 分子量: 340.424
• InChiKey: DLHXRJSTAJSMSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4-amino-2-(methylthio)thiazol-5-yl)(3,4,5- trimethoxyphenyl)methanone 在 氨 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以62%的产率得到(2,4-diamino-1,3-thiazol-5-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole: A unique, highly active antimicrotubule agent

  摘要：

  A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (31) inhibited at sub-micromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 31 is a promising new antimitotic agent with encouraging preclinical potential. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.013
• 作为产物：
  描述：

  在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 (4-amino-2-(methylthio)thiazol-5-yl)(3,4,5- trimethoxyphenyl)methanone
  参考文献：
  名称：

  NBS介导的从1,3-二羰基化合物和巯基腈盐顺序合成多官能噻唑和噻吩的一锅法

  摘要：

  由NBS介导的从1,3-二羰基化合物和硫醇腈盐开始的多官能噻唑和噻吩的顺序一锅法合成已经在温和的条件下进行。该转化涉及顺序溴化/ S N 2烷基化/索普-齐格勒环化/ -COR基团的区域选择性消除，以中等至良好的收率提供所需的产物。确定了-COR基团离去反应的顺序，并提出了可能的机制。

  DOI：

  10.1016/j.tetlet.2013.11.014

文献信息

• [EN] NOVEL BRIDGED BICYCLOALKYL-SUBSTITUTED AMINOTHIZOLES AND THEIR METHODS OF USE<br/>[FR] NOUVEAUX AMINOTHIAZOLES À SUBSTITUTION BICYCLOALKYLE PONTÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV TEMPLE

  公开号：WO2018136766A1

  公开（公告）日：2018-07-26

  The present invention includes novel bridged bicycloalkyl-substituted aminothiazole compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

  本发明涉及一种新颖的桥联双环烷基取代的氨基噻唑化合物，用于预防或治疗需要的患者的癌症。本发明还涉及通过向患者施用本发明化合物的治疗有效量来预防或治疗需要的患者的癌症的方法。
• Discovery and Optimization of a Series of 2-Aryl-4-Amino-5-(3′,4′,5′-trimethoxybenzoyl)Thiazoles as Novel Anticancer Agents
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Andrea Brancale、Xian-Hua Fu、Jun Li、Su-Zhan Zhang、Ernest Hamel、Roberta Bortolozzi、Elena Porcù、Giuseppe Basso、Giampietro Viola

  DOI：10.1021/jm300388h

  日期：2012.6.14

  inhibitors based on the 2-aryl/heteroaryl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole scaffold was synthesized and evaluated for growth inhibition activity on a panel of cancer cell lines, cell cycle effects, and in vivo potency. Structure–activity relationships were elucidated with various substitutions at the 2-position of the thiazole skeleton. Hydrophobic moieties, such as phenyl and 3-thienyl

  合成了一系列基于 2-aryl/heteroaryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazol 支架的微管蛋白聚合抑制剂，并评估了对一组癌细胞的生长抑制活性系、细胞周期效应和体内效力。通过噻唑骨架 2 位的各种取代阐明了构效关系。疏水部分，如苯基和 3-噻吩基，在该位置具有良好的耐受性，苯基取代基的变化对效力有显着影响。活性最强的化合物 ( 3b ) 通过线粒体途径诱导细胞凋亡，同时激活 caspase-3。我们还表明它具有潜在的抗血管活性，因为它在体外减少了在非细胞毒性浓度下内皮细胞迁移和毛细管样管形成中断。此外，化合物3b显着降低了裸鼠模型中 HT-29 异种移植物的生长，表明3b是一种有前途的新型抗有丝分裂剂，具有临床潜力。
• Bridged bicycloalkyl-substituted aminothiazoles and their methods of use
  申请人：Temple University—Of The Commonwealth System of Higher Education

  公开号：US10941126B2

  公开（公告）日：2021-03-09

  The present invention includes novel bridged bicycloalkyl-substituted aminothiazole compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

  本发明包括新型桥联双烷基取代氨基噻唑化合物，可用于预防或治疗有需要的受试者的癌症。本发明还包括通过向有需要的受试者施用治疗有效量的本发明化合物来预防或治疗癌症的方法。
• Novel Bridged Bicycloalkyl-Substituted Aminothiazoles and Their Methods of Use
  申请人：Temple University-Of The Commonwealth System of Higher Education

  公开号：US20190352272A1

  公开（公告）日：2019-11-21

  The present invention includes novel bridged bicycloalkyl-substituted aminothiazole compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.
• NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts
  作者：Laichun Luo、Lanlan Meng、Qi Sun、Zemei Ge、Runtao Li

  DOI：10.1016/j.tetlet.2013.11.014

  日期：2014.1

  A NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts has been developed under mild conditions. This transformation involves sequential bromination/SN2 alkylation/Thorpe–Ziegler cyclization/regio-selective elimination of a –COR group, affording the desired products in moderate to good yields. The sequence

  由NBS介导的从1,3-二羰基化合物和硫醇腈盐开始的多官能噻唑和噻吩的顺序一锅法合成已经在温和的条件下进行。该转化涉及顺序溴化/ S N 2烷基化/索普-齐格勒环化/ -COR基团的区域选择性消除，以中等至良好的收率提供所需的产物。确定了-COR基团离去反应的顺序，并提出了可能的机制。