5-hydroxy-2-(4-aminophenyl)-1,3-benzothiazole | 162374-51-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 5-hydroxy-2-(4-aminophenyl)-1,3-benzothiazole
• 英文别名: 5-Hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole；2-(4-aminophenyl)-1,3-benzothiazol-5-ol
• CAS: 162374-51-8
• 化学式: C₁₃H₁₀N₂OS
• 分子量: 242.301
• InChiKey: FVMBOPSVTWLWEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 5-hydroxy-2-(4-aminophenyl)-1,3-benzothiazole 在 silver trifluoromethanesulfonate 作用下， 以 丁酮 为溶剂， 生成 5-hydroxy-2-(4-(11C)methylaminophenyl)-1,3-benzothiazole
  参考文献：
  名称：

  탄소-11 표지 화합물의 고체상 추출을 통한 신속한 합성 방법.

  摘要：

  本发明涉及一种碳-11标记化合物的合成方法，包括：(a)合成[C11]碘化甲烷的步骤；(b)将所述[C11]碘化甲烷与去甲基前体反应以生成碳-11标记化合物的步骤；(c)包括将在步骤(b)中生成的碳-11标记化合物进行分离纯化的步骤。根据本发明，通过固相萃取碳-11标记化合物的分离纯化，可以大大缩短分离纯化时间，从而提高最终碳-11标记化合物的合成收率，相对于传统的高性能液相色谱法分离纯化。

  公开号：

  KR20200059528A
• 作为产物：
  描述：

  N-(3-methoxyphenyl)-4-nitrobenzamide 在 劳森试剂 、 六甲基磷酰三胺 、 sodium hydroxide 、 三溴化硼 、 tin(ll) chloride 、 potassium hexacyanoferrate(III) 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 11.5h， 生成 5-hydroxy-2-(4-aminophenyl)-1,3-benzothiazole
  参考文献：
  名称：

  Antitumor Benzothiazoles. 8. Synthesis, Metabolic Formation, and Biological Properties of the C- and N-Oxidation Products of Antitumor 2-(4-Aminophenyl)benzothiazoles

  摘要：

  2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC50 values (<0.1 mu M) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by la. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of la were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [C-14]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell Lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro.

  DOI：

  10.1021/jm990104o

文献信息

• Antitumor Benzothiazoles. 8. Synthesis, Metabolic Formation, and Biological Properties of the <i>C</i>- and <i>N</i>-Oxidation Products of Antitumor 2-(4-Aminophenyl)benzothiazoles
  作者：Eiji Kashiyama、Ian Hutchinson、Mei-Sze Chua、Sherman F. Stinson、Lawrence R. Phillips、Gurmeet Kaur、Edward A. Sausville、Tracey D. Bradshaw、Andrew D. Westwell、Malcolm F. G. Stevens

  DOI：10.1021/jm990104o

  日期：1999.10.1

  2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC50 values (<0.1 mu M) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by la. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of la were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [C-14]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell Lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro.
• 11C-labelled PIB analogues as potential tracer agents for in vivo imaging of amyloid β in Alzheimer's disease
  作者：K. Serdons、T. Verduyckt、D. Vanderghinste、P. Borghgraef、J. Cleynhens、F. Van Leuven、H. Kung、G. Bormans、A. Verbruggen

  DOI：10.1016/j.ejmech.2008.09.038

  日期：2009.4

  Pittsburgh Compound-B (PIB) is currently being evaluated clinically for in vivo visualization of amyloid plaques in patients with Alzheimer's disease (AD). We have synthesized three structural isomers of 6-hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole, performed radiolabelling with carbon-11 and investigated their in vivo and in vitro properties. Specific binding to amyloid plaques was demonstrated in vitro using post-mortem brain homogenates of AD patients, transgenic AD mice brain sections and postmortem human AD brain sections. In normal mice, initial brain uptake (at 2 min p.i.) was high and was followed by a fast wash-out. The three structural analogues have a high potential as tracer agents for in vivo visualization of amyloid plaques in AD patients. (C) 2008 Elsevier Masson SAS. All rights reserved.
• [EN] LIGANDS FOR AGGREGATED TAU MOLECULES<br/>[FR] LIGANDS POUR MOLÉCULES DE LA PROTÉINE TAU AGGLOMÉRÉES
  申请人：WISTA LAB LTD

  公开号：WO2010034982A1

  公开（公告）日：2010-04-01

  Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example:formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.
• Metabolically Stabilized Benzothiazoles for Imaging of Amyloid Plaques
  作者：Gjermund Henriksen、Andrea I. Hauser、Andrew D. Westwell、Behrooz H. Yousefi、Markus Schwaiger、Alexander Drzezga、Hans-Jürgen Wester

  DOI：10.1021/jm061466g

  日期：2007.3.1

  Six new N-C-11-labeled aminophenylbenzothiazoles substituted with fluorine in different positions have been synthesized and evaluated as amyloid-beta binding ligands. Our structure-property relationship studies show that the substitution pattern of the phenyl ring and the benzothiazole moiety has an influence on the metabolic stability, which in turn has an effect on the brain uptake kinetics. Two lead compounds have been identified with improved physicochemical characteristics for A beta-plaque imaging in vivo.
• 탄소-11 표지 화합물의 고체상 추출을 통한 신속한 합성 방법.
  申请人：Gachon University of Industry-Academic cooperation Foundation 가천대학교 산학협력단(220040376324) BRN ▼129-82-07687

  公开号：KR20200059528A

  公开（公告）日：2020-05-29

  본 발명은 탄소-11 표지 화합물의 합성 방법에 관한 것으로서, (a) [C11]요오드화 메탄을 합성하는 단계; (b) 데스메틸 전구체에 상기 [C11]요오드화 메탄을 반응시켜 탄소-11 표지 화합물을 생성하는 단계; (c) 상기 (b)단계에서 생성된 탄소-11 표지 화합물을 분리 정제하는 단계를 포함한다. 상기와 같은 본 발명에 따르면, 탄소-11 표지 화합물을 고체상 추출을 통해 분리 정제함으로써 기존의 고성능 액체 크로마토그래피로 분리 정제한 경우 보다 분리정제 시간이 훨씬 단축되어 최종 탄소-11 표지 화합물의 합성 수율을 증가시킬 수 있다.

  本发明涉及一种碳-11标记化合物的合成方法，包括：(a)合成[C11]碘化甲烷的步骤；(b)将所述[C11]碘化甲烷与去甲基前体反应以生成碳-11标记化合物的步骤；(c)包括将在步骤(b)中生成的碳-11标记化合物进行分离纯化的步骤。根据本发明，通过固相萃取碳-11标记化合物的分离纯化，可以大大缩短分离纯化时间，从而提高最终碳-11标记化合物的合成收率，相对于传统的高性能液相色谱法分离纯化。