(S)-2,6-diamino-N-(4-(5-fluorobenzothiazol-2-yl)-2-methylphenyl)hexanamide | 741241-36-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2,6-diamino-N-(4-(5-fluorobenzothiazol-2-yl)-2-methylphenyl)hexanamide
• 英文别名: phortress；(2S)-2,6-diamino-N-[4-(5-fluoro-1,3-benzothiazol-2-yl)-2-methylphenyl]hexanamide
• CAS: 741241-36-1
• 化学式: C₂₀H₂₃FN₄OS
• 分子量: 386.493
• InChiKey: LFDOEFHQLNGBQQ-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酰氯 在 劳森试剂 、 吡啶 、 tin(II) chloride dihdyrate 、 sodium hydride 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 六甲基磷酰三胺 、 乙醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 52.33h， 生成 (S)-2,6-diamino-N-(4-(5-fluorobenzothiazol-2-yl)-2-methylphenyl)hexanamide
  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

• 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.