N4-乙酰基磺胺苯吡唑 | 855-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: N4-乙酰基磺胺苯吡唑
• 中文别名: (1R,4a'S,5'R,7'R)-5'-羟基-3,3-二甲基-8'-甲亚基-1',9'-二羰基六氢螺[环己烷-1,4'-[2]氧杂[7,9a]亚甲基环庚三烯并[c]吡喃]-2-甲醛
• 英文名称: 4-(acetylamino)-N-(2-phenyl-2H-pyrazol-3-yl)benzenesulfonamide
• 英文别名: N-(4-(N-(1-phenyl-1H-pyrazol-5-yl)sulfamoyl)phenyl)acetamide；N⁴-Acetylsulfaphenazol；N4-Acetylsulfaphenazole；N-acetyl-sulfanilic acid-(2-phenyl-2H-pyrazol-3-ylamide)；N-Acetyl-sulfanilsaeure-(2-phenyl-2H-pyrazol-3-ylamid)；N-[4-[(2-phenylpyrazol-3-yl)sulfamoyl]phenyl]acetamide
• CAS: 855-91-4
• 化学式: C₁₇H₁₆N₄O₃S
• mdl: MFCD06015559
• 分子量: 356.405
• InChiKey: PSFOMYYDCTXBHG-UHFFFAOYSA-N

物化性质

• 熔点：
  >155°C (dec.)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N4-乙酰基磺胺苯吡唑 在 水 、 sodium hydroxide 作用下， 反应 2.0h， 以98%的产率得到磺胺苯吡唑
  参考文献：
  名称：

  磺胺苯唑衍生的功能化磺胺类药物对 CYP 2C9 抑制降低的结核分枝杆菌的优化和表征

  摘要：

  本研究通过系统优化抗菌药物磺胺苯唑，设计合成了一系列磺胺类化合物，用于治疗结核分枝杆菌（M.tuberculosis，M.tuberculosis）。初步结果表明，4-氨基苯磺酰胺部分在维持抗分枝杆菌活性方面起着关键作用。化合物10c、10d、10f和10i通过优化吡唑上R 2位点的苯环显示出良好的抗分枝杆菌活性和低细胞毒性。特别是，化合物10d显示出良好的活性（MIC = 5.69 μg/mL），对 CYP 2C9 的抑制（IC50  > 10 μM），因此药物相互作用的潜在风险较低。这些有希望的结果为使用磺胺作为治疗结核分枝杆菌的一种成分的联合方案提供了新的见解。

  DOI：

  10.1016/j.bmcl.2021.127924
• 作为产物：
  描述：

  5-氨基-4-乙氧羰基-1-苯基吡唑 在 硫酸 作用下， 生成 N4-乙酰基磺胺苯吡唑
  参考文献：
  名称：

  New aminobenzene sulfonamide

  摘要：

  公开号：

  US02858309A1

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.
• The optimization and characterization of functionalized sulfonamides derived from sulfaphenazole against Mycobacterium tuberculosis with reduced CYP 2C9 inhibition
  作者：Hui Chen、Bin Wang、Peng Li、Hong Yan、Gang Li、Haihong Huang、Yu Lu

  DOI：10.1016/j.bmcl.2021.127924

  日期：2021.5

  optimization on phenyl ring at the R2 site on the pyrazole displayed promising antimycobacterial activity paired with low cytotoxicity. In particular, compound 10d displayed good activity (MIC = 5.69 μg/mL) with low inhibition of CYP 2C9 (IC50 > 10 μM), consequently low potential risk of drug-drug interaction. These promising results provide new insight into the combination regimen using sulfonamide

  本研究通过系统优化抗菌药物磺胺苯唑，设计合成了一系列磺胺类化合物，用于治疗结核分枝杆菌（M.tuberculosis，M.tuberculosis）。初步结果表明，4-氨基苯磺酰胺部分在维持抗分枝杆菌活性方面起着关键作用。化合物10c、10d、10f和10i通过优化吡唑上R 2位点的苯环显示出良好的抗分枝杆菌活性和低细胞毒性。特别是，化合物10d显示出良好的活性（MIC = 5.69 μg/mL），对 CYP 2C9 的抑制（IC50  > 10 μM），因此药物相互作用的潜在风险较低。这些有希望的结果为使用磺胺作为治疗结核分枝杆菌的一种成分的联合方案提供了新的见解。
• New aminobenzene sulfonamide
  申请人：CIBA PHARM PROD INC

  公开号：US02858309A1

  公开（公告）日：1958-10-28