N-(3-hydroxypropyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide | 374632-67-4

• 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-(3-hydroxypropyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide
• CAS: 374632-67-4
• 化学式: C₂₄H₂₂N₄O₅S
• 分子量: 478.528
• InChiKey: OWBVFVPKTLCULA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-hydroxypropyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide 在 sodium dithionite 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以38%的产率得到4-(3-aminophenyl)-N-(3-hydroxypropyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Synthesis of Sulfaphenazole Derivatives and Their Use as Inhibitors and Tools for Comparing the Active Sites of Human Liver Cytochromes P450 of the 2C Subfamily

  摘要：

  Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes. These compounds are derived from SPA by replacement of the NH2 and H (of the SO2NH function) substituents of SPA with various R-1 and R-2 groups, respectively. Their inhibitory effects were studied on recombinant CYP 2C8, 2C9, 2C18, and 2C19 expressed in yeast. High affinities for CYP 2C9 (IC50 < 1 muM) were only observed for SPA derivatives having the SO2NH function and a relatively small R-1 substituent (R-1 = NH2, CH3). Any increase in the size of R-1 led to a moderate decrease of the affinity, and the N-alkylation of the SO2NH function of SPA to a greater decrease of this affinity. The same structural changes led to opposite effects on molecular recognition by CYP 2C8 and 2C18, which generally exhibited similar behaviors. Thus, contrary to CYP 2C9, CYP 2C8 and 2C18 generally prefer neutral compounds with relatively large R-1 and R2 substituents. CYP 2C19 showed an even lower affinity for anionic compounds than CYP 2C8 and 2C18. However, as CYP 2C8 and 2C18, CYP 2C19 showed a much better affinity for neutral compounds derived ftom N-alkylation of SPA and for anionic compounds bearing a larger R, substituent. One of the new compounds (R-1 = methyl, R-2 = propyl) inhibited all human CYP 2Cs with IC50 values between 10 and 20 muM, while another one (R-1 = allyl, R-2 = methyl) inhibited all CYP 2Cs except CYP 2C9, and a third one (R-1 = R-2 = methyl) inhibited all CYP 2Cs except CYP 2C8. Only 2 compounds of the 25 tested derivatives were highly selective toward one human CYP 2C; these are SPA and compound I (Ri = CH3, R2 = H), which acted as selective CYP 2C9 inhibitors. However, some SPA derivatives selectively inhibited CYP 2C8 and 2C18. Since CYP 2C18 is hardly detectable in human liver, these derivatives could be interesting molecules to selectively inhibit CYP 2C8 in human liver microsomes. Thus, compound 11 (R-1 = NH2, R-2 = (CH2)(2)CH(CH3)(2)) appears to be particularly interesting for that purpose as its IC50 value for CYP 2C8 is low (3 muM) and 20-fold smaller than those found for CYP 2C9 and 2C19.

  DOI：

  10.1021/jm010861y
• 作为产物：
  描述：

  3-硝基联苯 在 吡啶 、 氯磺酸 、 sodium hydroxide 、 sodium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 N-(3-hydroxypropyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Synthesis of Sulfaphenazole Derivatives and Their Use as Inhibitors and Tools for Comparing the Active Sites of Human Liver Cytochromes P450 of the 2C Subfamily

  摘要：

  Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes. These compounds are derived from SPA by replacement of the NH2 and H (of the SO2NH function) substituents of SPA with various R-1 and R-2 groups, respectively. Their inhibitory effects were studied on recombinant CYP 2C8, 2C9, 2C18, and 2C19 expressed in yeast. High affinities for CYP 2C9 (IC50 < 1 muM) were only observed for SPA derivatives having the SO2NH function and a relatively small R-1 substituent (R-1 = NH2, CH3). Any increase in the size of R-1 led to a moderate decrease of the affinity, and the N-alkylation of the SO2NH function of SPA to a greater decrease of this affinity. The same structural changes led to opposite effects on molecular recognition by CYP 2C8 and 2C18, which generally exhibited similar behaviors. Thus, contrary to CYP 2C9, CYP 2C8 and 2C18 generally prefer neutral compounds with relatively large R-1 and R2 substituents. CYP 2C19 showed an even lower affinity for anionic compounds than CYP 2C8 and 2C18. However, as CYP 2C8 and 2C18, CYP 2C19 showed a much better affinity for neutral compounds derived ftom N-alkylation of SPA and for anionic compounds bearing a larger R, substituent. One of the new compounds (R-1 = methyl, R-2 = propyl) inhibited all human CYP 2Cs with IC50 values between 10 and 20 muM, while another one (R-1 = allyl, R-2 = methyl) inhibited all CYP 2Cs except CYP 2C9, and a third one (R-1 = R-2 = methyl) inhibited all CYP 2Cs except CYP 2C8. Only 2 compounds of the 25 tested derivatives were highly selective toward one human CYP 2C; these are SPA and compound I (Ri = CH3, R2 = H), which acted as selective CYP 2C9 inhibitors. However, some SPA derivatives selectively inhibited CYP 2C8 and 2C18. Since CYP 2C18 is hardly detectable in human liver, these derivatives could be interesting molecules to selectively inhibit CYP 2C8 in human liver microsomes. Thus, compound 11 (R-1 = NH2, R-2 = (CH2)(2)CH(CH3)(2)) appears to be particularly interesting for that purpose as its IC50 value for CYP 2C8 is low (3 muM) and 20-fold smaller than those found for CYP 2C9 and 2C19.

  DOI：

  10.1021/jm010861y

文献信息

• Synthesis of Sulfaphenazole Derivatives and Their Use as Inhibitors and Tools for Comparing the Active Sites of Human Liver Cytochromes P450 of the 2C Subfamily
  作者：Nguyêt-Thanh Ha-Duong、Sylvie Dijols、Cristina Marques-Soares、Claire Minoletti、Patrick M. Dansette、Daniel Mansuy

  DOI：10.1021/jm010861y

  日期：2001.10.1

  Twenty-three new derivatives of sulfaphenazole (SPA) were synthesized to further explore the topology of the active sites of human liver cytochromes P450 of the 2C subfamily and to find new selective inhibitors of these cytochromes. These compounds are derived from SPA by replacement of the NH2 and H (of the SO2NH function) substituents of SPA with various R-1 and R-2 groups, respectively. Their inhibitory effects were studied on recombinant CYP 2C8, 2C9, 2C18, and 2C19 expressed in yeast. High affinities for CYP 2C9 (IC50 < 1 muM) were only observed for SPA derivatives having the SO2NH function and a relatively small R-1 substituent (R-1 = NH2, CH3). Any increase in the size of R-1 led to a moderate decrease of the affinity, and the N-alkylation of the SO2NH function of SPA to a greater decrease of this affinity. The same structural changes led to opposite effects on molecular recognition by CYP 2C8 and 2C18, which generally exhibited similar behaviors. Thus, contrary to CYP 2C9, CYP 2C8 and 2C18 generally prefer neutral compounds with relatively large R-1 and R2 substituents. CYP 2C19 showed an even lower affinity for anionic compounds than CYP 2C8 and 2C18. However, as CYP 2C8 and 2C18, CYP 2C19 showed a much better affinity for neutral compounds derived ftom N-alkylation of SPA and for anionic compounds bearing a larger R, substituent. One of the new compounds (R-1 = methyl, R-2 = propyl) inhibited all human CYP 2Cs with IC50 values between 10 and 20 muM, while another one (R-1 = allyl, R-2 = methyl) inhibited all CYP 2Cs except CYP 2C9, and a third one (R-1 = R-2 = methyl) inhibited all CYP 2Cs except CYP 2C8. Only 2 compounds of the 25 tested derivatives were highly selective toward one human CYP 2C; these are SPA and compound I (Ri = CH3, R2 = H), which acted as selective CYP 2C9 inhibitors. However, some SPA derivatives selectively inhibited CYP 2C8 and 2C18. Since CYP 2C18 is hardly detectable in human liver, these derivatives could be interesting molecules to selectively inhibit CYP 2C8 in human liver microsomes. Thus, compound 11 (R-1 = NH2, R-2 = (CH2)(2)CH(CH3)(2)) appears to be particularly interesting for that purpose as its IC50 value for CYP 2C8 is low (3 muM) and 20-fold smaller than those found for CYP 2C9 and 2C19.