2-(3-methyl-4-nitrosophenyl)-5-fluorobenzothiazole | 1384933-16-7

• 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-(3-methyl-4-nitrosophenyl)-5-fluorobenzothiazole
• CAS: 1384933-16-7
• 化学式: C₁₄H₉FN₂OS
• 分子量: 272.303
• InChiKey: WCFCPKFBGZGMES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  42.32
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酸 在 氯化亚砜 、 10% Pd/C 、 对甲苯磺酸 、 一水合肼 、 N,N-二甲基甲酰胺 、 三苯基膦 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 甲苯 为溶剂， 反应 33.5h， 生成 2-(3-methyl-4-nitrosophenyl)-5-fluorobenzothiazole
  参考文献：
  名称：

  Bioactivation of Fluorinated 2-Aryl-benzothiazole Antitumor Molecules by Human Cytochrome P450s 1A1 and 2W1 and Deactivation by Cytochrome P450 2S1

  摘要：

  Both 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (SF 203) and 5-fluoro-2-(3,4-dimethoxyphenyl)-benzothiazole (GW 610) contain the benzothiazole pharmacophore and possess potent and selective in vitro antitumor properties. Prior studies suggested the involvement of cytochrome P450 (P450) 1A1 and 2W1-mediated bioactivation in the antitumor activities and P450 2S1-mediated deactivation of 5F 203 and GW 610. In the present study, the biotransformation pathways of 5F 203 and GW 610 by P450s 1A1, 2W1, and 2S1 were investigated, and the catalytic parameters of P450 1A1- and 2W1-catalyzed oxidation were determined in steady-state kinetic studies. The oxidations of SF 203 catalyzed by P450s 1A1 and 2W1 yielded different products, and the formation of a hydroxylamine was observed for the first time in the latter process. Liquid chromatography-mass spectrometry (LC-MS) analysis with the synthetic hydroxylamine and also a P450 2W1/5F 203 incubation mixture indicated the formation of dGuo adduct via a putative nitrenium intermediate. P450 2W1-catalyzed oxidation of GW 610 was 5-fold more efficient than the P450 1A1-catalyzed reaction. GW 610 underwent a two-step oxidation process catalyzed by P450 1A1 or 2W1: a regiospecific O-demethylation and a further hydroxylation. Glutathione (GSH) conjugates of 5F 203 and GW 610, presumably through a quninoneimine and a 1,2-quinone intermediate, respectively, were detected. These results demonstrate that human P450s 1A1 and 2W1 mediate 5F 203 and GW 610 bioactivation to reactive intermediates and lead to GSH conjugates and a dGuo adduct, which may account for the antitumor activities of 5F 203 and GW 610 and also be involved in cell toxicity. P450 2S1 can catalyze the reduction of the hydroxylamine to the amine 5F 203 under anaerobic conditions and, to a lesser extent, under aerobic conditions, thus attenuating the anticancer activity.

  DOI：

  10.1021/tx3001994