4-氨基-N-乙基-N-苯基苯磺酰胺 | 50497-33-1

• 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: 4-氨基-N-乙基-N-苯基苯磺酰胺
• 英文名称: 4-amino-N-ethyl-N-phenylbenzene sulfonamide
• 英文别名: sulfanilic acid-(N-ethyl-anilide)；Sulfanilsaeure-(N-aethyl-anilid)；4-amino-N-ethyl-N-phenylbenzenesulfonamide
• CAS: 50497-33-1
• 化学式: C₁₄H₁₆N₂O₂S
• mdl: MFCD03615635
• 分子量: 276.359
• InChiKey: QMUIFGZYOIQAGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  4-氨基-N-乙基-N-苯基苯磺酰胺 在 盐酸 、 乙酸酐 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 43.0h， 生成
  参考文献：
  名称：

  Tikare, Ravindra K.; Badami, Bharati V.; Puranik, Gurubasav S., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1983, vol. 22, # 7, p. 673 - 677

  摘要：

  DOI：
• 作为产物：
  描述：

  N-ethyl-4-nitro-N-phenylbenzenesulfonamide 在 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以75%的产率得到4-氨基-N-乙基-N-苯基苯磺酰胺
  参考文献：
  名称：

  Sulfamoyl-4-oxoquinoline-3-carboxamides: Novel potentiators of defective ΔF508-cystic fibrosis transmembrane conductance regulator chloride channel gating

  摘要：

  The synthesis of a small collection of sulfamoyl-4-oxoquinoline-3-carboxamides is described for use as correctors of defective gating of the Delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Several compounds with submicromolar potency were obtained. N-Ethyl 6-(ethylphenylsulfamoyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (7b) was found to be the most effective sulfonamide corrector of defective Delta F508-CFTR gating. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.050

文献信息

• Phenylglycine and Sulfonamide Correctors of Defective ΔF508 and G551D Cystic Fibrosis Transmembrane Conductance Regulator Chloride-Channel Gating
  作者：Nicoletta Pedemonte、N. D. Sonawane、Alessandro Taddei、Jie Hu、Olga Zegarra-Moran、Yat Fan Suen、Lori I. Robins、Christopher W. Dicus、Dan Willenbring、Michael H. Nantz、Mark J. Kurth、Luis J. V. Galietta、A. S. Verkman

  DOI：10.1124/mol.105.010959

  日期：2005.5

  Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel cause cystic fibrosis. The ΔF508 mutation produces defects in channel gating and cellular processing, whereas the G551D mutation produces primarily a gating defect. To identify correctors of gating, 50,000 diverse small molecules were screened at 2.5 μM (with forskolin, 20 μM) by an iodide uptake assay in epithelial cells coexpressing ΔF508-CFTR and a fluorescent halide indicator (yellow fluorescent protein-H148Q/I152L) after ΔF508-CFTR rescue by 24-h culture at 27°C. Secondary analysis and testing of >1000 structural analogs yielded two novel classes of correctors of defective ΔF508-CFTR gating (“potentiators”) with nanomolar potency that were active in human ΔF508 and G551D cells. The most potent compound of the phenylglycine class, 2-[(2–1 H -indol-3-yl-acetyl)-methylamino]- N -(4-isopropylphenyl)-2-phenylacetamide, reversibly activated ΔF508-CFTR in the presence of forskolin with K a ∼ 70 nM and also activated the CFTR gating mutants G551D and G1349D with K a values of ∼1100 and 40 nM, respectively. The most potent sulfonamide, 6-(ethylphenylsulfamoyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid cycloheptylamide, had K a ∼ 20 nM for activation of ΔF508-CFTR. In cell-attached patch-clamp experiments, phenylglycine-01 (PG-01) and sulfonamide-01 (SF-01) increased channel open probability >5-fold by the reduction of interburst closed time. An interesting property of these compounds was their ability to act in synergy with cAMP agonists. Microsome metabolism studies and rat pharmacokinetic analysis suggested significantly more rapid metabolism of PG-01 than SF-03. Phenylglycine and sulfonamide compounds may be useful for monotherapy of cystic fibrosis caused by gating mutants and possibly for a subset of ΔF508 subjects with significant ΔF508-CFTR plasma-membrane expression.

  囊性纤维化跨膜传导调节器（CFTR）氯离子通道突变会导致囊性纤维化。ΔF508突变会产生通道门控和细胞处理缺陷，而G551D突变则主要产生门控缺陷。为了确定门控的校正因子，在上皮细胞中通过碘化物摄取测定筛选了 50,000 种不同的小分子，这些细胞共同表达了 ΔF508-CFTR 和一种荧光卤化物指示剂（黄色荧光蛋白-H148Q/I152L）。通过对超过 1000 种结构类似物进行二次分析和测试，发现了两类新型ΔF508-CFTR 门控缺陷校正器（"增效剂"），它们具有纳摩尔效力，在人类ΔF508 和 G551D 细胞中具有活性。苯甘氨酸类最有效的化合物 2-[(2-1H-吲哚-3-基乙酰基)-甲基氨基]-N-(4-异丙基苯基)-2-苯乙酰胺在福斯可林存在下可逆地激活了ΔF508-CFTR，K a ∼ 70 nM，还激活了 CFTR 门控突变体 G551D 和 G1349D，K a 值分别为 ∼ 1100 和 40 nM。最有效的磺酰胺是 6-（乙基苯基氨基磺酰基）-4-氧代-1,4-二氢喹啉-3-羧酸环庚酰胺，其激活 ΔF508-CFTR 的 K a ∼ 20 nM。在细胞附着贴片钳实验中，苯甘氨酸-01（PG-01）和磺胺-01（SF-01）通过减少爆发间关闭时间使通道开放概率增加了 5 倍以上。这些化合物的一个有趣特性是能与 cAMP 激动剂协同作用。微粒体代谢研究和大鼠药代动力学分析表明，PG-01 的代谢速度明显快于 SF-03。苯甘氨酸和磺酰胺化合物可能适用于由门控突变体引起的囊性纤维化的单药治疗，也可能适用于具有显著ΔF508-CFTR血浆膜表达的ΔF508受试者亚群。
• [EN] COMPOUNDS HAVING ACTIVITY IN INCREASING ION TRANSPORT BY MUTANT-CFTR AND USES THEREOF<br/>[FR] COMPOSES INTERVENANT DANS L'ACCELERATION DU TRANSPORT IONIQUE PAR LE CFTR MUTANT, ET UTILISATIONS DESDITS COMPOSES
  申请人：UNIV CALIFORNIA

  公开号：WO2005120497A3

  公开（公告）日：2006-12-14
• Irani, Current Science, 1945, vol. 14, p. 327
  作者：Irani

  DOI：——

  日期：——
• Tikare, R. K.; Dambal, D. B.; Pattanashetti, P. P., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1984, vol. 23, # 10, p. 1019 - 1020
  作者：Tikare, R. K.、Dambal, D. B.、Pattanashetti, P. P.、Badami, B. V.、Puranik, G. S.

  DOI：——

  日期：——
• TIKARE, RAVINDRA, K.;BADAMI, BHARATI, V.;PURANIK, GURUBASAV, S., INDIAN J. CHEM., 1983, 22, N 7, 673-677
  作者：TIKARE, RAVINDRA, K.、BADAMI, BHARATI, V.、PURANIK, GURUBASAV, S.

  DOI：——

  日期：——