2-<(4-Nitrophenyl)amino>benzoesaeure-methylester

• 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-Nitrophenyl)amino>benzoesaeure-methylester
• 英文别名: N-(4-nitrophenyl)anthranilic acid methyl ester；methyl 2-(4-nitrophenylamino)benzoate；2-[(4-Nitrophenyl)amino]benzoesaeure-methylester；Methyl 2-((4-nitrophenyl)amino)benzoate；methyl 2-(4-nitroanilino)benzoate
• 化学式: C₁₄H₁₂N₂O₄
• 分子量: 272.26
• InChiKey: ZHVGKTOZGNULGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-<(4-Nitrophenyl)amino>benzoesaeure-methylester 在 乙醇 、 sodium hydride 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 N-methoxy-2-(methyl(4-nitrophenyl)amino)benzamide
  参考文献：
  名称：

  由PhI（OAc）2介导的氧化C–N键形成2-（芳基氨基）苯甲酰胺构建1,4-苯二氮卓类骨架

  摘要：

  由2-（芳基氨基）苯甲酰胺通过PhI（OAc）2介导的氧化性C–N键形成，可方便地构建涉及具有重要生物学意义的1,4-苯并二氮杂skeleton骨架的新化合物。这种新的合成策略的吸引人的特征包括温和的反应条件，氧化偶联过程的不含重金属的特性以及可耐受广泛范围底物的灵活性。

  DOI：

  10.1021/jo402413g
• 作为产物：
  描述：

  2-(三氟甲基磺酰氧基)苯甲酸甲酯 、 4-硝基苯胺 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99%的产率得到2-<(4-Nitrophenyl)amino>benzoesaeure-methylester
  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

• Palladium-Catalyzed One-Step Synthesis of Isoindole-1,3-diones by Carbonylative Cyclization of <i>o</i>-Halobenzoates and Primary Amines
  作者：Shilpa A. Worlikar、Richard C. Larock

  DOI：10.1021/jo800936h

  日期：2008.9.19

  The palladium-catalyzed aminocarbonylation of o-halobenzoates produces 2-substituted isoindole-1,3-diones in good yields. This methodology provides a good one-step approach to this important class of heterocycles and tolerates a variety of functional groups, including methoxy, alcohol, ketone, and nitro groups.

  邻卤代苯甲酸酯的钯催化氨基羰基化反应以良好的收率生成 2-取代的异吲哚-1,3-二酮。该方法为这一类重要的杂环化合物提供了一种良好的一步法，并且可以耐受多种官能团，包括甲氧基、醇、酮和硝基。
• Hellwinkel, Dieter; Ittemann, Peter, Chemische Berichte, 1986, vol. 119, # 10, p. 3165 - 3197
  作者：Hellwinkel, Dieter、Ittemann, Peter

  DOI：——

  日期：——
• Construction of 1,4-Benzodiazepine Skeleton from 2-(Arylamino)benzamides through PhI(OAc)₂-Mediated Oxidative C–N Bond Formation
  作者：Xuming Li、Liu Yang、Xiang Zhang、Daisy Zhang-Negrerie、Yunfei Du、Kang Zhao

  DOI：10.1021/jo402413g

  日期：2014.2.7

  the biologically important 1,4-benzodiazepine skeleton were conveniently constructed from 2-(arylamino)benzamides through PhI(OAc)2-mediated oxidative C–N bond formation. The attractive features of this new synthetic strategy include mild reaction conditions, the heavy-metal-free characteristic of the oxidative coupling process, and the flexibility to tolerate a broad scope of substrates.

  由2-（芳基氨基）苯甲酰胺通过PhI（OAc）2介导的氧化性C–N键形成，可方便地构建涉及具有重要生物学意义的1,4-苯并二氮杂skeleton骨架的新化合物。这种新的合成策略的吸引人的特征包括温和的反应条件，氧化偶联过程的不含重金属的特性以及可耐受广泛范围底物的灵活性。
• 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.