4-[(2-phenylethyl)sulfamoyl]benzoic acid | 114958-23-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(2-phenylethyl)sulfamoyl]benzoic acid
• 英文别名: 4-[(2-phenylethyl)aminosulfonyl]-benzoic acid；4-(2-phenylethylsulfamoyl)benzoic acid
• CAS: 114958-23-5
• 化学式: C₁₅H₁₅NO₄S
• 分子量: 305.354
• InChiKey: WNEBHTSECDZNTM-UHFFFAOYSA-N

物化性质

• 沸点：
  518.4±60.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(2-phenylethyl)sulfamoyl]benzoic acid 在 吡啶 、 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-[(2-phenylethyl)aminosulfonyl]-benzamide
  参考文献：
  名称：

  Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent

  摘要：

  Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 mu M) and DHFR (IC50 = 1.8-19.8 mu M), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased similar to 8 and similar to 6 times than that of compound 1, respectively. Moreover, compound 20 exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.011
• 作为产物：
  描述：

  对甲苯磺酸 在 吡啶 、 potassium permanganate 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 14.0h， 生成 4-[(2-phenylethyl)sulfamoyl]benzoic acid
  参考文献：
  名称：

  Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent

  摘要：

  Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 mu M) and DHFR (IC50 = 1.8-19.8 mu M), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased similar to 8 and similar to 6 times than that of compound 1, respectively. Moreover, compound 20 exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.011

文献信息

• Synthesis and evaluation of multisubstrate inhibitors of an oncogene-encoded tyrosine-specific protein kinase. 1
  作者：Carolyn H. Kruse、Kenneth G. Holden、M. Lynn Pritchard、John A. Feild、David J. Rieman、Russell G. Greig、George Poste

  DOI：10.1021/jm00117a015

  日期：1988.9

  The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting multisubstrate inhibitors were tested for their ability to inhibit the transfer of phosphate

  描述了酪氨酸特异性蛋白激酶潜在的多底物抑制剂的合成和测试。底物之一，ATP，是由已知的激酶抑制剂5'-[4-（氟磺酰基）苯甲酰基]腺苷模拟的，后者通过磺酰基部分与酪氨酸模拟物共价连接。测试了所得的多底物抑制剂通过p60v-abl抑制磷酸从ATP转移到蛋白质受体的能力，p60v-abl是由Abelson鼠白血病病毒（A-MuLV）的转化基因（v-abl）编码的酪氨酸激酶。尽管一系列抑制剂显示出中等强度的活性（IC50值低至19 microM），酪氨酸模拟物的修饰没有产生大的影响，这表明它们不作为多底物抑制剂起作用，而是主要通过所有抑制剂共有的腺苷部分结合。通过发现抑制剂缺乏特异性，在相当的浓度下抑制丝氨酸激酶的发现，加强了这种解释。
• New Panx-1 Blockers: Synthesis, Biological Evaluation and Molecular Dynamic Studies
  作者：Letizia Crocetti、Gabriella Guerrini、Maria Paola Giovannoni、Fabrizio Melani、Silvia Lamanna、Lorenzo Di Cesare Mannelli、Elena Lucarini、Carla Ghelardini、Junjie Wang、Gerhard Dahl

  DOI：10.3390/ijms23094827

  日期：——

  that gave the best results as in our indole series (sulphonamide functions and one/two carboxylic groups) and in Panx-1 blockers reported in the literature (sulphonic acid). Compounds 4 and 13, the latter being an analogue of the drug Probenecid, are the most potent Panx-1 blockers obtained in this study, with I = 97% and I = 93.7% at 50 µM, respectively. Both compounds, tested in a mouse model of oxaliplatin-induced

  通道蛋白 Panx-1 与一些病理学有关，例如癫痫、缺血性中风、癌症和帕金森病以及神经性疼痛。这些观察结果使 Panx-1 成为一个有趣的生物靶标。我们之前发表了一些有效的吲哚衍生物作为 Panx-1 阻滞剂，作为该领域研究的延续，我们在此报告了对其他化学支架、萘和吡唑的研究，这些支架被适当地替换为那些在我们的吲哚中给出最佳结果的功能系列（磺酰胺官能团和一个/两个羧基）和文献中报道的 Panx-1 阻断剂（磺酸）。化合物 4 和 13（后者是丙磺舒药物的类似物）是本研究中获得的最有效的 Panx-1 阻滞剂，在 50 µM 浓度下，I 分别为 97% 和 93.7%。这两种化合物在奥沙利铂诱导的神经性疼痛小鼠模型中进行了测试，显示出相似的抗过敏特性，并且能够在注射 1 nmol 和 3 nmol 剂量后 45 分钟显着提高小鼠疼痛阈值。最后，分子动力学研究和主成分分析使得识别能够将活性化合
• Development and Characterization of Type I, Type II, and Type III LIM-Kinase Chemical Probes
  作者：Thomas Hanke、Sebastian Mathea、Julia Woortman、Eidarus Salah、Benedict-Tilman Berger、Anthony Tumber、Risa Kashima、Akiko Hata、Bernhard Kuster、Susanne Müller、Stefan Knapp

  DOI：10.1021/acs.jmedchem.2c01106

  日期：2022.10.13

  LIMKs has been linked to the development of diverse diseases, including cancers and cognitive disabilities, but well-characterized inhibitors known as chemical probes are still lacking. Here, we report the characterization of three highly selective LIMK1/2 inhibitors covering all canonical binding modes (type I/II/III) and the structure-based design of the type II/III inhibitors. Characterization of these

  LIMK 是肌动蛋白和微管动力学的重要调节剂，它们在许多细胞过程中发挥着重要作用。LIMKs 的放松管制与多种疾病的发展有关，包括癌症和认知障碍，但仍然缺乏被称为化学探针的充分表征的抑制剂。在这里，我们报告了三种高选择性 LIMK1/2 抑制剂的表征，涵盖所有典型结合模式（I/II/III 型）和 II/III 型抑制剂的基于结构的设计。这些化学探针的表征表明对 LIMK1/2 和所有抑制剂1（LIMKi3；I 型）、48（TH470；II 型）和15（TH257 ）具有低纳摩尔亲和力; III 型）在全面的 scanMAX 激酶选择性面板中显示出出色的选择性。磷酸化蛋白质组学显示，与变构抑制剂相比，I 型和 II 型抑制剂之间存在显着差异15。在脆弱 X 染色体的神经突长出模型等表型分析中，15显示出有前途的活性，表明变构 LIMK 抑制剂可用于治疗这种孤儿病。
• Design and synthesis of procollagen C-proteinase inhibitors
  作者：Eric Turtle、Nicholas Chow、Charles Yang、Sergio Sosa、Udo Bauer、Mitch Brenner、David Solow-Cordero、Wen-Bin Ho

  DOI：10.1016/j.bmcl.2012.10.067

  日期：2012.12

  Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from substrate leads. Compounds were optimized for potency and selectivity, with N-substituted aryl sulfonamide hydroxamates having the best combination of these properties. Compounds 89 and 60 have IC50 values of 10 and 80 nM, respectively, against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell-based collagen deposition assays. (C) 2012 Elsevier Ltd. All rights reserved.
• Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent
  作者：Huang Huang、Weiqiang Lu、Xi Li、Xiaoli Cong、Hongmei Ma、Xiaofeng Liu、Yu Zhang、Peng Che、Ruoqun Ma、Honglin Li、Xu Shen、Hualiang Jiang、Jin Huang、Jin Zhu

  DOI：10.1016/j.bmcl.2011.12.011

  日期：2012.1

  Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 mu M) and DHFR (IC50 = 1.8-19.8 mu M), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased similar to 8 and similar to 6 times than that of compound 1, respectively. Moreover, compound 20 exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design. (C) 2011 Elsevier Ltd. All rights reserved.