3-(4-氯苯基)-1-(4-甲氧基苯基)-1-亚硝基脲 | 87468-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(4-氯苯基)-1-(4-甲氧基苯基)-1-亚硝基脲
• 英文名称: 3-(4-chlorophenyl)-1-(4-methoxyphenyl)-1-nitrosourea
• 英文别名: N'-(4-Chlorophenyl)-N-(4-methoxyphenyl)-N-nitrosourea
• CAS: 87468-14-2
• 化学式: C₁₄H₁₂ClN₃O₃
• 分子量: 305.721
• InChiKey: CKIXKIDZQYUSEI-UHFFFAOYSA-N

物化性质

• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-氯苯基)-1-(4-甲氧基苯基)-1-亚硝基脲 、 2-萘酚 以 乙醇 为溶剂， 反应 72.0h， 以15.8%的产率得到1-(4-methoxyphenylazo)naphthalen-2-ol
  参考文献：
  名称：

  Action mechanism of anti-AH13 activity of 1,3-diaryl-1-nitrosoureas and related compounds.

  摘要：

  1,3-二芳基-1-亚硝基脲（I）的给药延长了经腹腔注射腹水肝癌AH13细胞的大鼠的寿命。化合物I产生的活性物质为芳基重氮离子、芳基异氰酸酯和亚硝阳离子。这些物质与腺苷、鸟苷、L-赖氨酸以及N-乙 acetyl-DL-青霉胺的巯基反应。1,3-二芳基-1-亚硝基脲的可能抗AH13作用机制被提出如下：亚硝基脲（I）迅速渗透到细胞质或细胞核中，并分解产生活性中间体，即芳基重氮离子，与肿瘤细胞的核酸反应形成脱氧核糖核酸（DNA）加成物，从而导致肿瘤细胞死亡。释放自化合物I的芳基异氰酸酯和亚硝阳离子抑制其它受损细胞的DNA修复，它们与修复酶反应形成氨基甲酰化和S-亚硝基化的酶。

  DOI：

  10.1248/cpb.32.564
• 作为产物：
  描述：

  1-(4-氯苯基)-3-(4-甲氧基苯基)脲 在 亚硝酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(4-氯苯基)-3-(4-甲氧基苯基)-1-亚硝基脲 、 3-(4-氯苯基)-1-(4-甲氧基苯基)-1-亚硝基脲
  参考文献：
  名称：

  Substituent effects on nitrosation of 1,3-diarylureas with nitrosyl chloride, dinitrogen trioxide, and dinitrogen tetroxide.

  摘要：

  制备了28个对位取代和11个邻位取代的1,3-二芳基脲。测得的质子核磁共振（1H-NMR）谱图用于评估对位取代脲脲基质子的酸性并估计邻位取代分子的构象。两个脲基质子的化学位移和酸度受1,3-二芳基脲中两个对位取代基的加和性控制。16个对位取代二芳基脲与气体亚硝化试剂（三氧化二氮、四氧化二氮或亚硝酰氯）经亚硝化反应得到不稳定的1,3-二芳基-1-亚硝基脲[R1-C6H4-N(NO)-CO-NH-C6H4-R2]和1,3-二芳基-3-亚硝基脲[R1-C6H4-NH-CO-N(NO)-C6H4-R2]异构体混合物。每种亚硝化脲的异构体比例与原始脲1H-NMR谱图中两个脲基质子化学位移差（d[NH]）相关。当d[NH]低于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，获得了较好的线性关系（r(NOCl) = 0.943，n = 11；r(N2O3) = 0.869，n = 15）。当d[NH]高于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，1-亚硝化异构体[R1-C6H4-N(NO)-CO-NH-C6H4-R2]是唯一产物。这些原理不能扩展到四氧化二氮。13个对位取代二芳基脲仅得到1-或3-亚硝化脲基衍生物作为唯一产物，只有4个得到亚硝化异构体混合物。测定了5种邻位取代1,3-二芳基脲的1H-NMR谱图用于构象分析。它们的构象似乎与对位取代二芳基脲不同。11个邻位取代1,3-二芳基脲与亚硝酰氯和四氧化二氮进行亚硝化反应。在许多情况下，亚硝基主要引入空间位阻较小的脲基氮，得到了1-和3-亚硝化脲的异构体混合物。

  DOI：

  10.1248/cpb.34.1950

文献信息

• Substituent effects on nitrosation of 1,3-diarylureas with nitrosyl chloride, dinitrogen trioxide, and dinitrogen tetroxide.
  作者：MAKOTO MIYAHARA

  DOI：10.1248/cpb.34.1950

  日期：——

  Twenty-eight para-substituted and eleven ortho-substituted 1, 3-diarylureas were prepared.Their proton nuclear magnetic resonance (1H-NMR) spectra were measured to evaluate the acidity of the ureido protons in the para-substituted ureas, and to estimate the conformations of ortho-substituted molecules. The chemical shifts and acidities of two ureido protons were additively controlled by the two para-substituents in the 1, 3-diarylureas. The sixteen para-substitued diarylureas were nitrosated with gaseous nitrosating reagents (dinitrogen trioxide, dinitrogen tetroxide or nitroxyl chloride) to give unstable isomeric mixtures of 1, 3-diaryl-1-nitrosoureas [R1-C6H4-N(NO)-CO-NH-C6H4-R2] and 1, 3-diaryl-3-nitrosoureas [R1-C6H4-NH-CO-N(NO)-C6H4-R2]. The isomer ratio of each nitrosated urea was correlated with the difference between the chemical shifts (d[NH]) of the two ureido protons in the 1H-NMR spectrum of the starting urea. When d[NH] was below 0.25 ppm (with NOCl) or 0.45 ppm (with N2O3), good linearity was obtained (r(NOCl)=0.943, n=11; r(N2O3)=0.869, n=15). When d[NH] was over 0.25 ppm (NOCl) or 0.45 ppm (N2O3), the 1-nitrosated isomer [R1-C6H4-N(NO)-CO-NH-C6H4-R2] was the sole product. These principles ould not be extended to dinitrogen tetroxide.Thirteen para-substituted diarylureas gave 1- or 3-nitrosated ureido derivatives as sole products and only four gave nitrosated isomeric mixtures.The 1H-NMR spectra of 5 types of ortho-substituted 1, 3-diarylureas were measured for comformational analysis. Their conformations seem to be different from those of para-substituted diarylureas. Eleven ortho-substituted 1, 3-diarylureas were nitrosated with nitrosyl chloride and dinitrogen tetroxide. In many cases, the nitroso group was predominantly introduced at the ureido nitrogen, which is less hindered sterically, and isomeric mixtures of 1- and 3-nitrosated ureas were obtained.

  制备了28个对位取代和11个邻位取代的1,3-二芳基脲。测得的质子核磁共振（1H-NMR）谱图用于评估对位取代脲脲基质子的酸性并估计邻位取代分子的构象。两个脲基质子的化学位移和酸度受1,3-二芳基脲中两个对位取代基的加和性控制。16个对位取代二芳基脲与气体亚硝化试剂（三氧化二氮、四氧化二氮或亚硝酰氯）经亚硝化反应得到不稳定的1,3-二芳基-1-亚硝基脲[R1-C6H4-N(NO)-CO-NH-C6H4-R2]和1,3-二芳基-3-亚硝基脲[R1-C6H4-NH-CO-N(NO)-C6H4-R2]异构体混合物。每种亚硝化脲的异构体比例与原始脲1H-NMR谱图中两个脲基质子化学位移差（d[NH]）相关。当d[NH]低于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，获得了较好的线性关系（r(NOCl) = 0.943，n = 11；r(N2O3) = 0.869，n = 15）。当d[NH]高于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，1-亚硝化异构体[R1-C6H4-N(NO)-CO-NH-C6H4-R2]是唯一产物。这些原理不能扩展到四氧化二氮。13个对位取代二芳基脲仅得到1-或3-亚硝化脲基衍生物作为唯一产物，只有4个得到亚硝化异构体混合物。测定了5种邻位取代1,3-二芳基脲的1H-NMR谱图用于构象分析。它们的构象似乎与对位取代二芳基脲不同。11个邻位取代1,3-二芳基脲与亚硝酰氯和四氧化二氮进行亚硝化反应。在许多情况下，亚硝基主要引入空间位阻较小的脲基氮，得到了1-和3-亚硝化脲的异构体混合物。
• Action mechanism of anti-AH13 activity of 1,3-diaryl-1-nitrosoureas and related compounds.
  作者：MICHIKO MIYAHARA、MAKOTO MIYAHARA、SHOZO KAMIYA

  DOI：10.1248/cpb.32.564

  日期：——

  Administration of 1, 3-diaryl-1-nitrosoureas (I) prolonged the life span of rats inoculated intraperitoneally with ascites hepatoma AH13 cells. Active species produced from compound I were aryl diazonium ion, aryl isocyanate and nitrosonium ion. These species reacted with adenine, guanine, L-lysine, and the SH group of N-acetyl-DL-penicillamine. A possible anti-AH13 action mechanism of 1, 3-diaryl-1-nitrosoureas in proposed to be as follows. The nitrosoureas (I) permeate quickly into the cytoplasm or nucleus, and decompose to give an active intermediate, an aryl diazonium ion, which reacts with nucleic acids of tumor cells to form a deoxyribonucleic acid (DNA) adduct, followed by tumor cell death. DNA repair of other damaged cells is inhibited by aryl isocyanate and nitrosonium ion liberated from compound I, which reacts with repair enzyme to form carbamoylated and S-nitrosated enzyme.

  1,3-二芳基-1-亚硝基脲（I）的给药延长了经腹腔注射腹水肝癌AH13细胞的大鼠的寿命。化合物I产生的活性物质为芳基重氮离子、芳基异氰酸酯和亚硝阳离子。这些物质与腺苷、鸟苷、L-赖氨酸以及N-乙 acetyl-DL-青霉胺的巯基反应。1,3-二芳基-1-亚硝基脲的可能抗AH13作用机制被提出如下：亚硝基脲（I）迅速渗透到细胞质或细胞核中，并分解产生活性中间体，即芳基重氮离子，与肿瘤细胞的核酸反应形成脱氧核糖核酸（DNA）加成物，从而导致肿瘤细胞死亡。释放自化合物I的芳基异氰酸酯和亚硝阳离子抑制其它受损细胞的DNA修复，它们与修复酶反应形成氨基甲酰化和S-亚硝基化的酶。