2-[4-(methoxycarbonyl)phenylamino]benzoic acid methyl ester

• 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: 2-[4-(methoxycarbonyl)phenylamino]benzoic acid methyl ester
• 英文别名: N-(4-(methoxycarbonyl)phenyl)anthranilic acid methyl ester；Methyl 2-(4-methoxycarbonylanilino)benzoate
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: LAAXBJBCXDFYSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-(methoxycarbonyl)phenylamino]benzoic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 N-(4-羧基苯基)邻氨基苯甲酸
  参考文献：
  名称：

  基于邻氨基苯甲酸的运甲状腺素蛋白淀粉样蛋白原纤维抑制剂的合成和评价。

  摘要：

  合成八个小分子以评估N-取代邻氨基苯甲酸的结构活性关系（SAR）。通过邻氨基苯甲酸甲酯的苄基化或芳基化合成分子。基于光散射的淀粉样蛋白原纤维形成试验用于评估体外转甲状腺素蛋白（TTR）淀粉样蛋白原纤维形成的潜在抑制剂。间羧基苯基化和邻三氟甲基苯基化的邻氨基苯甲酸是有效的抑制剂，将经受进一步的SAR和结构分析。

  DOI：

  10.1016/s0960-894x(98)00696-9
• 作为产物：
  描述：

  2-(三氟甲基磺酰氧基)苯甲酸甲酯 、 4-氨基苯甲酸甲酯 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 以90%的产率得到2-[4-(methoxycarbonyl)phenylamino]benzoic acid methyl ester
  参考文献：
  名称：

  Development of Potent and Selective Inhibitors of Aldo–Keto Reductase 1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase) Based on N-Phenyl-Aminobenzoates and Their Structure–Activity Relationships

  摘要：

  Aldo-keto reductase 1C3 (AKR1C3; type 5 17 beta-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5 alpha-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of Sa-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.

  DOI：

  10.1021/jm201547v

文献信息

• Bis-substituted diphenylamine arylidene hydrazones for the synthesis of new binuclear organotin(IV) complexes: Crystal structure, DNA cleavage and molecular docking
  作者：Maryam Yousefi、Tahereh Sedaghat、Jim Simpson、Hossein Motamedi、Mohammad Reza Dayer

  DOI：10.1016/j.poly.2018.08.040

  日期：2018.11

  Abstract Five dinuclear organotin(IV) complexes, R4Sn2La (R = Me, Ph) and R4Sn2Lb (R = Me, Ph and Bu) have been synthesized from reaction of R2SnCl2 with 2,4′- and 2,2′-bis-substituted diphenylamine arylidene hydrazones, H4La and H4Lb, respectively. The synthesized compounds have been investigated by elemental analysis and IR, 1H NMR, and 119Sn NMR spectroscopy. The structures of Me4Sn2Lb and Ph4Sn2Lb have

  摘要通过R2SnCl2与2,4'-和2,2'-双取代反应合成了五种双核有机锡（IV）配合物R4Sn2La（R = Me，Ph）和R4Sn2Lb（R = Me，Ph和Bu）二苯胺亚芳基，分别为H4La和H4Lb。合成的化合物已通过元素分析和IR，1H NMR和119Sn NMR光谱进行了研究。Me4Sn2Lb和Ph4Sn2Lb的结构也已通过X射线晶体学证实。结果表明，完全去质子化的双hydr配体提供了两个连续的ONO三齿结构域，它们与烯醇盐形式的两个SnR2部分配位。配合物中的每个锡原子均采用五配位环境。配体和复合物对革兰氏阳性菌（枯草芽孢杆菌和金黄色葡萄球菌）和革兰氏阴性菌（大肠杆菌和铜绿假单胞菌）均没有抗菌活性。然而，发现配体及其甲基复合物均可降解DNA，这一观察结果与分子对接所提示的相互作用方式相适应。
• Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors
  作者：Vibha B Oza、H.Michael Petrassi、Hans E Purkey、Jeffery W Kelly

  DOI：10.1016/s0960-894x(98)00696-9

  日期：1999.1

  Eight small molecules were synthesized to evaluate the structure activity relationships (SAR) of N-substituted anthranilic acids. The molecules were synthesized by benzylation or arylation of methyl anthranilate. A light scattering-based amyloid fibril formation assay was used to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. The m-carboxyphenylated and o-t

  合成八个小分子以评估N-取代邻氨基苯甲酸的结构活性关系（SAR）。通过邻氨基苯甲酸甲酯的苄基化或芳基化合成分子。基于光散射的淀粉样蛋白原纤维形成试验用于评估体外转甲状腺素蛋白（TTR）淀粉样蛋白原纤维形成的潜在抑制剂。间羧基苯基化和邻三氟甲基苯基化的邻氨基苯甲酸是有效的抑制剂，将经受进一步的SAR和结构分析。
• Synthesis and biological evaluation of novel 2,4′-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors
  作者：Sahar Mahmoud Abou-Seri

  DOI：10.1016/j.ejmech.2010.05.072

  日期：2010.9

  Four new series of 2,4'-bis diphenylamine hydrazones 14, 2,4'-bis aminothiadiazole 16, 2,4'-bis mercaptotriazole 17-18 and 2,4'-bis mercapto-oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-2-[4(5-(ethylamino)-1,3,4-thiadiazol-2-yl)- phenylaminolphenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 mu M). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC50 values ranging 0.73-2.38 mu M. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Development of Potent and Selective Inhibitors of Aldo–Keto Reductase 1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase) Based on <i>N</i>-Phenyl-Aminobenzoates and Their Structure–Activity Relationships
  作者：Adegoke O. Adeniji、Barry M. Twenter、Michael C. Byrns、Yi Jin、Mo Chen、Jeffrey D. Winkler、Trevor M. Penning

  DOI：10.1021/jm201547v

  日期：2012.3.8

  Aldo-keto reductase 1C3 (AKR1C3; type 5 17 beta-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5 alpha-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of Sa-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.