4-[4-(4-chlorophenyl)piperazin-1-yl]-3-pyridinesulfonamide | 1491138-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[4-(4-chlorophenyl)piperazin-1-yl]-3-pyridinesulfonamide
• 英文别名: 4-[4-(4-Chlorophenyl)-1-piperazinyl]-3-pyridinesulfonamide；4-[4-(4-chlorophenyl)piperazin-1-yl]pyridine-3-sulfonamide
• CAS: 1491138-67-0
• 化学式: C₁₅H₁₇ClN₄O₂S
• 分子量: 352.845
• InChiKey: BBKFOQCRDAHPDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.53
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-[4-(4-chlorophenyl)piperazin-1-yl]-3-pyridinesulfonamide 在 potassium carbonate 、 potassium hydroxide 作用下， 以 丙酮 为溶剂， 反应 34.25h， 生成 N-(5-amino-1H-1,2,4-triazol-3-yl)-4-[4-(4-chlorophenyl)piperazin-1-yl]pyridine-3-sulfonamide
  参考文献：
  名称：

  具有潜在抗真菌活性的新型4位取代的N-（5-氨基-1H-1,2,4-三唑-3-基）吡啶-3-磺酰胺衍生物的合成。

  摘要：

  念珠菌病对免疫反应改变的患者构成严重威胁。因此，我们已经进行了包含吡啶-3-磺酰胺支架和已知的抗真菌活性的1,2,4-三唑取代基的化合物的合成。因此，已经通过从4-氯吡啶-3-磺酰胺开始的多步反应合成了一系列新颖的4-取代的N-（5-氨基-1H-1,2,4-三唑-3-基）吡啶-3-磺酰胺。 N′-氰基-N-[（4-取代的吡啶-3-基）磺酰基]氨基甲硫代氨基甲酸酯，其进一步与水合肼转化为相应的1,2,4-三唑衍生物26-36。评估了最终化合物对分离自真菌病患者的念珠菌，大脚草属，杜鹃花属和酿酒酵母属菌株的抗真菌活性。其中许多药物显示出比氟康唑更大的功效，主要针对白色念珠菌和粘菌Rhodotorula mucilaginosa，MIC值≤25 µg / mL。进行了对活性最高的化合物26、34和35的对接研究，显示了与白色念珠菌羊毛甾醇14α-脱甲基酶结合的潜在模式。NCI-60细胞系还评估了所选化合物的体外细胞毒性。

  DOI：

  10.3390/molecules22111926
• 作为产物：
  描述：

  4-氯吡啶-3-磺酰胺 、 1-(4-chlorophenyl)piperazine dihydrochloride 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以62%的产率得到4-[4-(4-chlorophenyl)piperazin-1-yl]-3-pyridinesulfonamide
  参考文献：
  名称：

  Carbonic anhydrase inhibitors. Synthesis of heterocyclic 4-substituted pyridine-3-sulfonamide derivatives and their inhibition of the human cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII

  摘要：

  A series of novel heterocyclic 4-substituted pyridine-3-sulfonamides 2-13,15-20 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC4.2.1.1), that is the cytosolic CA I and II, and tumor-associated isozymes CA IX and XII. Against the human isozymes hCA I the new compounds showed K-I values in the range 169-5400 nM, toward hCA II in range 58.5-1238 nM, against hCA IX in range 19.5-652 nM and against hCA XII in the range of 16.8-768 nM. Compounds 15-19 representing 4-(1H-pyrazol-1-yl)-3-pyridinesulfonamide derivatives showed good hCA IX inhibitory efficacy with K-I = 19.5-48.6 nM comparable or more effective than clinically used sulfonamides: AAZ, MZA, EZA, DCP, IND (K-I = 24-50 nM). Anticancer evaluation at a single dose 10 mu M, against a panel of 60 human tumor cell lines, was performed at the US National Cancer Institute, on compounds 2, 3, 5-13, 16,17, 19, 20. Among them 6 bearing 4-(3,4,-dichlorophenyl)piperazine moiety showed broad spectrum of growth inhibition in the range 25-89% over 26 cell lines representing all tumors subpanels. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.027

文献信息

• Synthesis of Novel 1-(4-Substituted pyridine-3-sulfonyl)-3-phenylureas with Potential Anticancer Activity
  作者：Krzysztof Szafrański、Jarosław Sławiński

  DOI：10.3390/molecules200712029

  日期：——

  A series of novel 4-substituted-N-(phenylcarbamoyl)-3-pyridinesulfonamides 11–27 have been synthesized by the reaction of 4-substituted pyridine-3-sulfonamides 2–10 with the appropriate aryl isocyanates in presence of potassium carbonate. The in vitro anticancer activity of compounds 11, 12, 14–21 and 24–26 was evaluated at the U.S. National Cancer Institute and in light of the results, some structure-activity relationships were discussed. The most prominent compound, N-[(4-chlorophenyl)carbamoyl]-4-[4-(3,4-dichlorophenyl)piperazin-1-yl]pyridine-3-sulfonamide (21) has exhibited a good activity profile and selectivity toward the subpanels of leukemia, colon cancer and melanoma, with average GI50 values ranging from 13.6 to 14.9 µM.

  在碳酸钾存在下，4-取代吡啶-3-磺酰胺类化合物 2-10 与适当的芳基异氰酸酯反应，合成了一系列新型 4-取代-N-（苯基氨基甲酰基）-3-吡啶磺酰胺类化合物 11-27。美国国家癌症研究所对 11、12、14-21 和 24-26 号化合物的体外抗癌活性进行了评估，并根据评估结果讨论了一些结构-活性关系。其中最突出的化合物 N-[(4-氯苯基)氨基甲酰基]-4-[4-(3,4-二氯苯基)哌嗪-1-基]吡啶-3-磺酰胺（21）对白血病、结肠癌和黑色素瘤等亚型癌症具有良好的活性和选择性，平均 GI50 值为 13.6 至 14.9 µM。
• Carbonic anhydrase inhibitors. Synthesis of heterocyclic 4-substituted pyridine-3-sulfonamide derivatives and their inhibition of the human cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII
  作者：Jarosław Sławiński、Krzysztof Szafrański、Daniela Vullo、Claudiu T. Supuran

  DOI：10.1016/j.ejmech.2013.09.027

  日期：2013.11

  A series of novel heterocyclic 4-substituted pyridine-3-sulfonamides 2-13,15-20 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC4.2.1.1), that is the cytosolic CA I and II, and tumor-associated isozymes CA IX and XII. Against the human isozymes hCA I the new compounds showed K-I values in the range 169-5400 nM, toward hCA II in range 58.5-1238 nM, against hCA IX in range 19.5-652 nM and against hCA XII in the range of 16.8-768 nM. Compounds 15-19 representing 4-(1H-pyrazol-1-yl)-3-pyridinesulfonamide derivatives showed good hCA IX inhibitory efficacy with K-I = 19.5-48.6 nM comparable or more effective than clinically used sulfonamides: AAZ, MZA, EZA, DCP, IND (K-I = 24-50 nM). Anticancer evaluation at a single dose 10 mu M, against a panel of 60 human tumor cell lines, was performed at the US National Cancer Institute, on compounds 2, 3, 5-13, 16,17, 19, 20. Among them 6 bearing 4-(3,4,-dichlorophenyl)piperazine moiety showed broad spectrum of growth inhibition in the range 25-89% over 26 cell lines representing all tumors subpanels. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Syntheses of Novel 4-Substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamide Derivatives with Potential Antifungal Activity
  作者：Krzysztof Szafrański、Jarosław Sławiński、Anna Kędzia、Ewa Kwapisz

  DOI：10.3390/molecules22111926

  日期：——

  via N'-cyano-N-[(4-substitutedpyridin-3-yl)sulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26-36. The final compounds were evaluated for antifungal activity against strains of the genera Candida, Geotrichum, Rhodotorula, and Saccharomycess isolated from patients with mycosis. Many of them show greater efficacy than fluconazole

  念珠菌病对免疫反应改变的患者构成严重威胁。因此，我们已经进行了包含吡啶-3-磺酰胺支架和已知的抗真菌活性的1,2,4-三唑取代基的化合物的合成。因此，已经通过从4-氯吡啶-3-磺酰胺开始的多步反应合成了一系列新颖的4-取代的N-（5-氨基-1H-1,2,4-三唑-3-基）吡啶-3-磺酰胺。 N′-氰基-N-[（4-取代的吡啶-3-基）磺酰基]氨基甲硫代氨基甲酸酯，其进一步与水合肼转化为相应的1,2,4-三唑衍生物26-36。评估了最终化合物对分离自真菌病患者的念珠菌，大脚草属，杜鹃花属和酿酒酵母属菌株的抗真菌活性。其中许多药物显示出比氟康唑更大的功效，主要针对白色念珠菌和粘菌Rhodotorula mucilaginosa，MIC值≤25 µg / mL。进行了对活性最高的化合物26、34和35的对接研究，显示了与白色念珠菌羊毛甾醇14α-脱甲基酶结合的潜在模式。NCI-60细胞系还评估了所选化合物的体外细胞毒性。