2-(4-amino-3-cyanophenyl)benzothiazole | 178804-13-2

• 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: 2-(4-amino-3-cyanophenyl)benzothiazole
• 英文别名: 2-amino-5-(1,3-benzothiazol-2-yl)benzonitrile
• CAS: 178804-13-2
• 化学式: C₁₄H₉N₃S
• 分子量: 251.312
• InChiKey: KANSGSDVVOUGAX-UHFFFAOYSA-N

物化性质

• 沸点：
  480.7±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 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：
  90.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-amino-3-cyanophenyl)benzothiazole 在 硫酸 作用下， 反应 2.0h， 生成 2-(4-amino-3-carboxyphenyl)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
• 作为产物：
  描述：

  4-(2-苯并噻唑基)苯胺 在 一氯化碘 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 2-(4-amino-3-cyanophenyl)benzothiazole
  参考文献：
  名称：

  Antitumor Benzothiazoles. 3. Synthesis of 2-(4-Aminophenyl)benzothiazoles and Evaluation of Their Activities against Breast Cancer Cell Lines in Vitro and in Vivo

  摘要：

  A new series of 2-(4-aminophenyl)benzothiazoles substituted in the phenyl ring and benzothiazole moiety has been synthesized by simple, high-yielding routes. The parent molecule 5a shows potent inhibitory activity in vitro in the nanomolar range against a panel of human breast cancer cell lines, but is inactive (IC50 > 30 mu M) against other cell types: activity against the sensitive breast lines MCF-7 and MDA 468 is characterized by a biphasic dose-response relationship. Structure-activity relationships derived using these cell types has revealed that activity follows the heterocyclic sequence benzothiazole > benzoxazole much greater than benzimidazole and that 2-(4-aminophenyl)benzothiazoles bearing a 3'-methyl- 9a, 3'-bromo- 9c, 3'- iodo- 9f, and 3'-chloro-substituent 9i are especially potent and their activity extends to ovarian, lung, and renal cell lines. Four compounds have been evaluated in vivo against human mammary carcinoma models in nude mice. Compound 9a showed the most potent growth inhibition against the ER(+) (MCF-7 and BO) and ER(-) (MT-1 and MT-3) tumors. Our efforts to identify a pharmacological mechanism of action for these intriguing compounds have not, as yet, been successful.

  DOI：

  10.1021/jm9600959

文献信息

• Design and synthesis of three series of novel antitumor–azo derivatives
  作者：Phoebe F. Lamie、John N. Philoppes

  DOI：10.1007/s00044-017-1839-4

  日期：2017.6

  Three new series of thiazoles, quinolones, and thiazolidinones merged with benzimidazole, benzoxazole, and benzothiazole nuclei were synthesized. The compounds were subjected to Infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, mass spectrometry, and elemental analyses. Cytotoxic activity of compounds were evaluated against breast (MCF-7) and colon (HCT-116) cell lines. Seven

  合成了三类新的噻唑，喹诺酮和噻唑烷酮与苯并咪唑，苯并恶唑和苯并噻唑核合并。对化合物进行红外，1 H核磁共振，13 C核磁共振，质谱和元素分析。评估了化合物对乳腺（MCF-7）和结肠（HCT-116）细胞系的细胞毒活性。七个化合物的IC 50值为0.0112至0.0198 µM，因此比参考药物阿霉素更有效（ 针对MCF-7和HCT-116的IC 50分别为0.0084和0.0088 µM）。
• 2-arylbenzazole compounds
  申请人：Cancer Research Campaign Technology Limited

  公开号：US06034246A1

  公开（公告）日：2000-03-07

  There are disclosed herein 2-phenylbenzazole compounds having a 3'-substituent and a 4'-NR.sup.2 R.sup.6 substituent in the phenyl group where R.sup.5 and R.sup.6 are each hydrogen or alkyl, or where the $'-NR.sup.5 R.sup.6 substituent is N-acyl (or N-benzoyl). There are also disclosed 2-phenylbenzazole compounds in the form of 4'-N sulphamate salts. Such compounds exhibit significant selective cytotoxic activity in respect of tumor cells and provide potentially useful chemotherapeutic agents for selective treatment of a range of cancers.

  本文披露了一种具有3'-取代基和4'-NR.sup.2 R.sup.6 取代基的2-苯基苯并咪唑化合物，其中R.sup.5和R.sup.6分别为氢或烷基，或者$'-NR.sup.5 R.sup.6 取代基为N-酰基（或N-苯甲酰基）。还披露了以4'-N磺酰酸盐形式存在的2-苯基苯并咪唑化合物。这些化合物在肿瘤细胞方面表现出显著的选择性细胞毒性活性，并提供了潜在有用的化疗药物，用于选择性治疗一系列癌症。
• Design and synthesis of new benzoxazole/benzothiazole-phthalimide hybrids as antitumor-apoptotic agents
  作者：John N. Philoppes、Phoebe F. Lamie

  DOI：10.1016/j.bioorg.2019.102978

  日期：2019.8

  Herein, we synthesized a series of twelve benzoxazole and benzothiazole derivatives incorporated with phthalimide core as anticancer agents. The most active compounds were 5a and 5g against HepG2 and MCF7 cell lines with IC50 = 0.011 and 0.006 mu M, respectively.They evaluated against EGFR and HER2 enzymes. From cell cycle analysis, it was observed that test compounds exerted pre G1 apoptosis and cell cycle arrest at G2/M phase. The achieved results suggested that apoptosis was due to activation of caspase-7 and caspase-9. EGFR was chosen as a biological target for carrying molecular modeling study for the newly synthesized compounds.
• Antitumour benzothiazoles. Part 20: 3′-Cyano and 3′-Alkynyl-Substituted 2-(4′-Aminophenyl)benzothiazoles as new potent and selective analogues
  作者：Ian Hutchinson、Tracey D Bradshaw、Charles S Matthews、Malcolm F.G Stevens、Andrew D Westwell

  DOI：10.1016/s0960-894x(02)00930-7

  日期：2003.2

  The synthesis of a new series of antitumour 2-(4-aminophenyl)benzothiazole analogues, substituted in the 3'-position by cyano or alkynyl groups, is described. Several of the analogues, notably the 5-fluorinated compounds 7c and 9c, were found to possess potent in vitro activity against MCF-7 and MDA 468 human cancer cell lines. More comprehensive in vitro analysis (NCI 60-cell line) established compound 7c as a particularly potent and selective 2-(4-aminophenyl)benzothiazole analogue. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 2-ARYLBENZAZOLE COMPOUNDS
  申请人：Cancer Research Ventures Limited

  公开号：EP0812319B1

  公开（公告）日：2002-07-10