N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide | 343975-60-0

• 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: N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide
• 英文别名: Benzamide, n-(2-bromo-5-fluorophenyl)-3-methyl-4-nitro-
• CAS: 343975-60-0
• 化学式: C₁₄H₁₀BrFN₂O₃
• 分子量: 353.147
• InChiKey: GTRSNUOGWMOXTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide 在 劳森试剂 、 tin(II) chloride dihdyrate 、 sodium hydride 作用下， 以 N-甲基吡咯烷酮 、 六甲基磷酰三胺 、 乙醇 、 mineral oil 为溶剂， 反应 25.0h， 生成 化合物5-FLUORO203
  参考文献：
  名称：

  Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; synthesis of 5F203 hydrogels for local delivery

  摘要：

  Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R-2 > 0.7). Time-dependent appearance of gamma-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.052
• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酸 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(2-bromo-5-fluorophenyl)-3-methyl-4-nitrobenzamide
  参考文献：
  名称：

  Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; synthesis of 5F203 hydrogels for local delivery

  摘要：

  Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R-2 > 0.7). Time-dependent appearance of gamma-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.052

文献信息

• Antitumor Benzothiazoles. 14. Synthesis and in Vitro Biological Properties of Fluorinated 2-(4-Aminophenyl)benzothiazoles
  作者：Ian Hutchinson、Mei-Sze Chua、Helen L. Browne、Valentina Trapani、Tracey D. Bradshaw、Andrew D. Westwell、Malcolm F. G. Stevens

  DOI：10.1021/jm001104n

  日期：2001.4.1

  Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluorobenzothiazoles were formed from the established Jacobsen cyclization of precursor 3-fluorothiobenzanilides, two modifications to this general process have allowed the synthesis of pure samples of these target compounds. Fluorinated 2-(4-aminophenyl)benzothiazoles were potently cytotoxic (GI(50) < 1 nM) in vitro in sensitive human breast MCF-7 (ER+) and MDA 468 (ER-) cell lines but inactive (GI(50) > 10 muM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT 116 colon cells. The biphasic dose-response relationship characteristically shown by the benzothiazole series against sensitive cell lines was exhibited by the 4- and 6-fluorobenzothiazoles (10b,d) but not by the 5- and 7-fluoro-benzothiazoles (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the g-fluoro isomer (10d), produces no exportable metabolites in the presence of sensitive MCF-7 cells. Induction of cytochrome P450 CYP1A1, a crucial event in determining the antitumor specificity of this series of benzothiazoles, was not compromised. 10h is currently the focus of pharmaceutical and preclinical development.
• Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; synthesis of 5F203 hydrogels for local delivery
  作者：Erica L. Stone、Francesca Citossi、Rajinder Singh、Balvinder Kaur、Margaret Gaskell、Peter B. Farmer、Anne Monks、Curtis Hose、Malcolm F.G. Stevens、Chee-Onn Leong、Michael Stocks、Barrie Kellam、Maria Marlow、Tracey D. Bradshaw

  DOI：10.1016/j.bmc.2015.09.052

  日期：2015.11

  Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R-2 > 0.7). Time-dependent appearance of gamma-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines. (C) 2015 Elsevier Ltd. All rights reserved.