2-(N-苄基-4-甲基苯基磺酰胺)乙酸 | 20158-69-4

• 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: 2-(N-苄基-4-甲基苯基磺酰胺)乙酸
• 中文别名: N-苄基-N-[(4-甲基苯基)磺酰基]甘氨酸
• 英文名称: 2-(N-benzyl-4-methylphenylsulfonamido)acetic acid
• 英文别名: N-benzyl-N-[(4-methylphenyl)sulfonyl]glycine；N-benzyl-N-(toluene-4-sulfonyl)-glycine；N-Benzyl-N-(toluol-4-sulfonyl)-glycin；p-Toluolsulfonsaeure-carboxymethylbenzylamid；N-p-Toluolsulfonyl-N-benzyl-glycin；N-(4-methylbenzenesulfonyl)-N-benzylglycine；2-[benzyl-(4-methylphenyl)sulfonylamino]acetic acid
• CAS: 20158-69-4
• 化学式: C₁₆H₁₇NO₄S
• mdl: MFCD00531206
• 分子量: 319.381
• InChiKey: KVTANZMSACMJTP-UHFFFAOYSA-N

物化性质

• 熔点：
  141 °C
• 沸点：
  524.8±60.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  2-(N-苄基-4-甲基苯基磺酰胺)乙酸 在 三氯化铝 、 氯化亚砜 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 4-<2-(3-methoxyphenyl)ethyl>-3-tosyl-1,2,3,4-tetrahydro-4-isoquinolol
  参考文献：
  名称：

  Rozhkov, V. S.; Sladkov, V. I.; Turdybekov, K. M., Journal of Organic Chemistry USSR (English Translation), 1989, vol. 25, # 6.2, p. 1162 - 1167

  摘要：

  DOI：
• 作为产物：
  描述：

  苄胺 在 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-(N-苄基-4-甲基苯基磺酰胺)乙酸
  参考文献：
  名称：

  Progresses in the pursuit of aldose reductase inhibitors: The structure-based lead optimization step

  摘要：

  Aldose reductase (ALR2) is a crucial enzyme in the development of the major complications of diabetes mellitus. Very recently it has been demonstrated that the ARL2 inhibitor, fidarestat, significantly prevents inflammatory signals (TNF-alpha, LPS) that cause cancer (colon, breast, prostate and lung), metastasis, asthma, and other inflammatory diseases. Currently, fidarestat is in phase Ill clinical trial for diabetic neuropathy and was found to be safe. Thus the finding of novel, potent ARL2 inhibitors is today more than in the past in great demand as they can pave the way for a novel therapeutic approach for a number of diseases besides the diabetes. Herein, starting from the virtual screening-derived ALR2 inhibitor S12728 (1), a rational receptor-based lead optimization has been undertaken. The design and synthetic efforts here reported led to the discovery of several new compounds endowed with low micromolar/submicromolar activities. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.045

文献信息

• HIV protease inhibitors based on amino acid derivatives
  申请人：——

  公开号：US20020151546A1

  公开（公告）日：2002-10-17

  A compound selected from the group consisting of a compound of formula I 1 a compound of formula II 2 and when the compound of formula I and II comprises an amino group pharmaceutically acceptable ammonium salts thereof, wherein R 1 , R 2 , Cx, n, R 3 , R 4 , R 5 , Y are as defined in the specification.

  从以下组中选择的化合物，其中化合物I的化合物，化合物II的化合物，以及当化合物I和II的化合物包括其氨基团的药用可接受铵盐，其中R1、R2、Cx、n、R3、R4、R5、Y的定义如规范中所述。
• Protease inhibitors – Part 5. Alkyl/arylsulfonyl- and arylsulfonylureido-/arylureido- glycine hydroxamate inhibitors of Clostridium histolyticum collagenase
  作者：A Scozzafava

  DOI：10.1016/s0223-5234(00)00127-6

  日期：2000.3

  Reaction of alkyl/arylsulfonyl halides with glycine afforded a series of derivatives which were first N-benzylated by treatment with benzyl chloride, and then converted to the corresponding hydroxamic acids with hydroxylamine in the presence of carbodiimide derivatives. Other derivatives were obtained by reaction of N-benzyl-glycine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate

  烷基/芳基磺酰基卤化物与甘氨酸反应得到一系列衍生物，其首先通过用苄基氯处理而被N-苄基化，然后在碳二亚胺衍生物存在下用羟胺转化成相应的异羟肟酸。如上所述，通过使N-苄基-甘氨酸与芳基异氰酸酯，芳基磺酰基异氰酸酯或苯甲酰基异硫氰酸酯反应，然后将它们的COOH基团转化为CONHOH部分，可获得其他衍生物。分析了这里报道的90种新化合物作为溶组织梭状芽孢杆菌胶原酶（EC 3.4.24.3）的抑制剂，这是一种锌酶，可降解天然胶原的三个螺旋区域。所制备的异羟肟酸酯衍生物的活性通常比相应的羧酸盐高100-500倍。在一系列合成异羟肟酸酯中，导致最佳抑制剂的取代模式是涉及全氟烷基磺酰基和取代的芳基磺酰基部分的那些，例如五氟苯基磺酰基，3-和4-羧基苯基磺酰基-，3-三氟甲基-苯基磺酰基或1-和2-萘基。因此，似乎与基质金属蛋白酶（MMP）异羟肟酸酯抑制剂相似，溶组织梭状芽孢杆菌胶原酶抑制剂应在P（1'）
• Solid Phase Synthesis of N-Alkyl Sulfonamides
  作者：Sharon Dankwardt、David Smith、John Porco Jr.、Cindy Nguyen

  DOI：10.1055/s-1997-5776

  日期：1997.7

  Polymer-supported sulfonamides were alkylated using alkyl halides in the presence of DBU or with alcohols via the Mitsunobu reaction.

  聚合物支撑的磺酰胺在 DBU 存在下使用烷基卤化物进行烷基化，或通过 Mitsunobu 反应与醇进行烷基化。
• Development of new N-arylbenzamides as STAT3 dimerization inhibitors
  作者：Murali K. Urlam、Roberta Pireddu、Yiyu Ge、Xiaolei Zhang、Ying Sun、Harshani R. Lawrence、Wayne C. Guida、Saïd M. Sebti、Nicholas J. Lawrence

  DOI：10.1039/c3md20323a

  日期：——

  The O-tosylsalicylamide S3I-201 (10) was used as a starting point for design and synthesis of novel STAT-3 dimerization inhibitors with improved drug-like qualities. The phosphonic acid 12d and salicylic acids 13f, 13g with a shorter amide linker lacking the O-tosyl group had improved STAT-3 inhibitory activity. The equivalent potencies observed by the replacement of phosphonic acid moiety of 12d with 5-amino-2-hydroxybenzoic acid group as in 13f further validates 5-amino-2-hydroxybenzoic acid as a phosphotyrosine mimic. The salicylic acid 13f displayed improved whole cell activity. The focused library of salicylic acids 13 with benzamide linker indicated that hydrophobic heptyl and cyclohexyl are the best tolerated R groups and a biphenyl ether (as the Ar group) significantly contributes to STAT3 inhibitory activity. Our docking studies indicated that the acidic groups of 12d, 13f and 13g interact in the p-Tyr-705 binding site in a broadly similar manner, while the phenoxybenzoyl group and the cyclohexylbenzyl group occupying pY+1 and pY−X hydrophobic pockets respectively. The in vitro and cell based potency of 13f warrants further development of this scaffold as STAT3 inhibitors.

  O-甲苯磺酰水杨酰胺 S3I-201 (10) 被用作设计和合成新型 STAT-3 二聚化抑制剂的起点，该抑制剂具有改进的药物样品质。具有缺少O-甲苯磺酰基的较短酰胺连接体的膦酸12d和水杨酸13f、13g具有改善的STAT-3抑制活性。通过用 13f 中的 5-氨基-2-羟基苯甲酸基团替换 12d 的膦酸部分观察到的等效效力进一步验证了 5-氨基-2-羟基苯甲酸作为磷酸酪氨酸模拟物。水杨酸 13f 显示出改善的全细胞活性。带有苯甲酰胺连接体的水杨酸 13 的聚焦文库表明，疏水性庚基和环己基是耐受性最好的 R 基团，而联苯醚（作为 Ar 基团）对 STAT3 抑制活性有显着贡献。我们的对接研究表明，12d、13f 和 13g 的酸性基团以大致相似的方式在 p-Tyr-705 结合位点中相互作用，而苯氧基苯甲酰基和环己基苄基分别占据 pY+1 和 pY−X 疏水袋。 13f 的体外和基于细胞的效力保证了该支架作为 STAT3 抑制剂的进一步开发。
• [EN] STAT3 DIMERIZATION INHIBITORS<br/>[FR] INHIBITEURS DE DIMÉRISATION DE STAT3
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2014070859A1

  公开（公告）日：2014-05-08

  The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

  本文所披露的主题涉及组成物的制备和使用方法。在进一步的方面，本文所披露的主题涉及STAT3二聚化抑制剂。还揭示了制备这些组成物的方法以及包含这些组成物的组合物。还揭示了通过向需要的个体投与所披露的化合物的有效量来治疗或预防某些癌症的方法。此外，本文还揭示了通过将细胞与本文所披露的化合物或组合物接触以抑制STAT3的方法。