ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate | 1100715-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate
• 英文别名: Ethyl 1-(3-nitrophenyl)-5-phenyl-3-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl]pyrazole-4-carboxylate
• CAS: 1100715-25-0
• 化学式: C₂₁H₁₇N₇O₇S₂
• 分子量: 543.541
• InChiKey: QTLWPNSAVMHPEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  242
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate 在 sodiumsulfide nonahydrate 、 sulfur 、 盐酸 、 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以76%的产率得到ethyl 1-(3-aminophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazole-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Effects of new 5-amino-1,3,4-thiadiazole-2-sulfonamide derivatives on human carbonic anhydrase isozymes

  摘要：

  Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1 (inhibitor 1) were synthesized from 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride compounds. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (AAZ), and of 16 newly synthesized amides (8-11, 12a-f, 13a-c, 14a-b, and 15) on hydratase and esterase activities of these isoenzymes have been studied in vitro. The average IC50 values of the new compounds (8-11,12a-f, 13a-c, 14a-b, and 15) for hydratase activity ranged from 3.25 to 4.75 mu M for hCA-I and from 0.055 to 2.6 mu M for hCA-II. The mean IC50 values of the same inhibitors for esterase activity were in the range of 2.7-6.6 mu M for hCA-I ( with the exception of inhibitor 10, which did not inhibit the esterase activity of hCA-I) and of 0.013-4.2 mu M for hCA-II. The K-i values for new compounds (8-11, 12a-f, 13a-c, 14a-b, and 15) were observed well below that of the parent compound inhibitor 1 and were also comparable to that of AAZ under the same experimental conditions. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives preferentially inhibit hCA-II and are more potent inhibitors of hCA-II than the parent inhibitor 1 and AAZ. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.048
• 作为产物：
  描述：

  5-氨基-1,3,4-噻二唑-2-磺酰胺 、 4-(ethoxycarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid 在 氯化亚砜 作用下， 生成 ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide

  摘要：

  Pyrazole carboxylic acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide (inhibitor 1) were synthesized from ethyl 3-(chlorocarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-4-carboxylate compound. The inhibitory effects of inhibitor 1, acetazolamide (AAZ) and of 11 newly synthesized amides (5a-b, 6, 7a-g, and 8) on hydratase and esterase activities of carbonic anhydrase isoenzymes (hCA-I and hCA-II) have been studied in vitro. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives inhibit CA isoenzymes and they are more potent inhibitors than the parent inhibitor 1 and AAZ. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.041

文献信息

• Synthesis and characterisation of novel Co(II) complexes of pyrazole carboxylate derivated of sulfonamide as carbonic anhydrase inhibitors
  作者：Nurgün Büyükkidan、Bülent Büyükkidan、Metin Bülbül、Rahmi Kasimoğullari、Murat Serdar、Samet Mert

  DOI：10.1111/j.2042-7158.2012.01609.x

  日期：2013.1.29

  Two new metal complexes, diaquabis(4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide)cobalt(II) dihydrate (2) and diaquabis(ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate)cobalt(II) monohydrate (4), containing sulfonamide have been synthesized by the reaction of Co(II) with 4-benzoyl-1,5-diphenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3-carboxamide (1) and ethyl-1-(3-nitrophenyl)-5-phenyl-3-(5-sulfamoyl-1,3,4-thiadiazol-2-ylcarbamoyl)-1H-pyrazole-4-carboxylate (3), respectively.

  The structures of Co(II) complexes 2 and 4 have been characterised by spectroscopic methods and elemental analyses. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of ligands 3 and 4, acetazolamide as a control compound and the newly synthesized complexes on the activity of hydratase and esterase of these isoenzymes have been studied in vitro.

  The concentration of compounds 2 and 4 producing a 50% inhibition of hydratase activity (IC50 values) were 0.473 ± 0.025 and 0.065 ± 0.002 μm for hCA-I and 0.213 ± 0.015 and 0.833 ± 0.021 μm for hCA-II, respectively. The IC50 values of synthesized compounds 2 and 4 for esterase activity were, 0.058 ± 0.006 and 0.297 ± 0.015 μm for hCA-I and 0.110 ± 0.010 and 0.052 ± 0.002 μm for hCA-II, respectively. In relation to esterase activity, the inhibition equilibrium constants (Ki) were determined as 0.039 ± 0.004 and 0.247 ± 0.035 μm on hCA-I and 0.078 ± 0.002 and 0.363 ± 0.015 μm on hCA-II for 2 and 4, respectively.

  The synthesized compounds 2 and 4 had effective inhibitory activity (P < 0.0001) on hCA-I and hCA-II than the corresponding free ligands, 1 and 3, and acetazolamide. Compounds 2 and 4 might be considered as potential inhibitors.

  摘要 本研究合成了两种新的含磺酰胺的金属配合物，分别为二水合物二(4-苯甲酰-1,5-二苯基-N-(5-磺酰基-1,3,4-噻二唑-2-基)-1H-吡唑-3-羧酰胺)钴(II) (2) 和单水合物二(乙基-1-(3-硝基苯基)-5-苯基-3-(5-磺酰基-1,3,4-噻二唑-2-基甲酰基)-1H-吡唑-4-羧酸乙酯)钴(II) (4)，分别通过Co(II)与4-苯甲酰-1,5-二苯基-N-(5-磺酰基-1,3,4-噻二唑-2-基)-1H-吡唑-3-羧酰胺(1)和乙基-1-(3-硝基苯基)-5-苯基-3-(5-磺酰基-1,3,4-噻二唑-2-基甲酰基)-1H-吡唑-4-羧酸乙酯(3)反应合成。 利用光谱方法和元素分析表征了Co(II)配合物2和4的结构。通过亲和色谱从红细胞中纯化了人类碳酸酐酶同工酶(hCA-I和hCA-II)。研究了配体3和4、作为对照化合物的乙酰唑胺以及新合成的配合物对这些同工酶的水合酶和酯酶活性的体外抑制作用。 配合物2和4在hCA-I和hCA-II的水合酶活性50%抑制浓度(IC50值)分别为0.473±0.025和0.065±0.002 μm以及0.213±0.015和0.833±0.021 μm。合成的配合物2和4对酯酶活性的IC50值分别为0.058±0.006和0.297±0.015 μm以及0.110±0.010和0.052±0.002 μm。关于酯酶活性，配合物2和4在hCA-I上的抑制平衡常数(Ki)分别为0.039±0.004和0.247±0.035 μm，在hCA-II上分别为0.078±0.002和0.363±0.015 μm。 合成的配合物2和4对hCA-I和hCA-II的抑制活性(P < 0.0001)均高于相应的自由配体1和3以及乙酰唑胺，因此可能被视为潜在的抑制剂。
• Synthesis, characterization and<i>in vitro</i>inhibition of metal complexes of pyrazole based sulfonamide on human erythrocyte carbonic anhydrase isozymes I and II
  作者：Nurgün Büyükkıdan、Bülent Büyükkıdan、Metin Bülbül、Rahmi Kasımoğulları、Samet Mert

  DOI：10.1080/14756366.2016.1247056

  日期：2017.1.1

  compounds. A sulfonamide possessing carbonic anhydrase (CA) inhibitory properties obtained from a pyrazole based sulfonamide, ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate (1), and its metal complexes with the Ni(II) for (2), Cu(II) for (3) and Zn(II) for (4) have been synthesized. The structures of metal complexes (2-4) were established on the

  磺酰胺代表重要的一类生物活性化合物。从吡唑基磺酰胺乙基1-（3-硝基苯基）-5-苯基-3-（（5-氨磺酰基-1,3,4-噻二唑-2-基）乙基获得的具有碳酸酐酶（CA）抑制特性的磺酰胺合成了（1）的氨基甲酰基）-1H-吡唑-4-羧酸盐（1）及其与（2）的Ni（II），（3）的Cu（II）和（4）的Zn（II）的金属配合物。根据元素分析，1 H NMR，IR，UV-Vis和MS光谱数据建立了金属配合物（2-4）的结构。使用水合酶和酯酶测定法体外研究了两种人碳酸酐酶（hCA，EC 4.2.1.1）同工酶I和II对1和合成的配合物（2-4）和乙酰唑胺（AAZ）作为对照化合物的抑制作用。配合物2、3和4在0范围内显示抑制常数。
• Effects of new 5-amino-1,3,4-thiadiazole-2-sulfonamide derivatives on human carbonic anhydrase isozymes
  作者：Rahmi Kasımoğulları、Metin Bülbül、Hatice Günhan、Hülya Güleryüz

  DOI：10.1016/j.bmc.2009.03.048

  日期：2009.5

  Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1 (inhibitor 1) were synthesized from 4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride compounds. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by the affinity chromatography. The inhibitory effects of inhibitor 1, acetazolamide (AAZ), and of 16 newly synthesized amides (8-11, 12a-f, 13a-c, 14a-b, and 15) on hydratase and esterase activities of these isoenzymes have been studied in vitro. The average IC50 values of the new compounds (8-11,12a-f, 13a-c, 14a-b, and 15) for hydratase activity ranged from 3.25 to 4.75 mu M for hCA-I and from 0.055 to 2.6 mu M for hCA-II. The mean IC50 values of the same inhibitors for esterase activity were in the range of 2.7-6.6 mu M for hCA-I ( with the exception of inhibitor 10, which did not inhibit the esterase activity of hCA-I) and of 0.013-4.2 mu M for hCA-II. The K-i values for new compounds (8-11, 12a-f, 13a-c, 14a-b, and 15) were observed well below that of the parent compound inhibitor 1 and were also comparable to that of AAZ under the same experimental conditions. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives preferentially inhibit hCA-II and are more potent inhibitors of hCA-II than the parent inhibitor 1 and AAZ. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis, characterization and antiglaucoma activity of some novel pyrazole derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide
  作者：Rahmi Kasımoğulları、Metin Bülbül、B. Seçkin Arslan、Başak Gökçe

  DOI：10.1016/j.ejmech.2010.07.041

  日期：2010.11

  Pyrazole carboxylic acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide (inhibitor 1) were synthesized from ethyl 3-(chlorocarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-4-carboxylate compound. The inhibitory effects of inhibitor 1, acetazolamide (AAZ) and of 11 newly synthesized amides (5a-b, 6, 7a-g, and 8) on hydratase and esterase activities of carbonic anhydrase isoenzymes (hCA-I and hCA-II) have been studied in vitro. The comparison of newly synthesized amides to inhibitor 1 and to AAZ indicated that the new derivatives inhibit CA isoenzymes and they are more potent inhibitors than the parent inhibitor 1 and AAZ. (C) 2010 Elsevier Masson SAS. All rights reserved.