3-[N-(4-氯苯基)氨基]苯甲酸甲酯 | 1055975-68-2

• 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: 3-[N-(4-氯苯基)氨基]苯甲酸甲酯
• 英文名称: 3-[N-(4-chlorophenyl)amino]benzoic acid methyl ester
• 英文别名: methyl 3-((4-chlorophenyl)amino)benzoate；3-[(4-chlorophenyl)amino]benzoic acid methyl ester；methyl 3-(4-chloroanilino)benzoate
• CAS: 1055975-68-2
• 化学式: C₁₄H₁₂ClNO₂
• 分子量: 261.708
• InChiKey: XPEWNZJBTHHIJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 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：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[N-(4-氯苯基)氨基]苯甲酸甲酯 在 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以81%的产率得到3-[N-(4-chlorophenyl)amino]benzoic acid
  参考文献：
  名称：

  Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3)

  摘要：

  Aldo-keto reductase 1C3 (AKR1C3) also known as type 5 17 beta-hydroxysteroid dehydrogenase has been implicated as one of the key enzymes driving the elevated intratumoral androgen levels observed in castrate resistant prostate cancer (CRPC). AKR1C3 inhibition therefore presents a rational approach to managing CRPC. Inhibitors should be selective for AKR1C3 over other AKR1C enzymes involved in androgen metabolism. We have synthesized 2-, 3-, and 4-(phenylamino)benzoic acids and identified 3-(phenylamino) benzoic acids that have nanomolar affinity and exhibit over 200-fold selectivity for AKR1C3 versus other AKR1C isoforms. The AKR1C3 inhibitory potency of the 4'-substituted 3-(phenylamino)benzoic acids shows a linear correlation with both electronic effects of substituents and the pK(a) of the carboxylic acid and secondary amine groups, which are interdependent. These compounds may be useful in treatment and/or prevention of CRPC as well as understanding the role of AKR1C3 in endocrinology. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.010
• 作为产物：
  描述：

  3-溴苯甲酸甲酯 、 对氯苯胺 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52%的产率得到3-[N-(4-氯苯基)氨基]苯甲酸甲酯
  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

• Reductive C−N Coupling of Nitroarenes: Heterogenization of MoO ₃ Catalyst by Confinement in Silica
  作者：Fu Yang、Xuexue Dong、Yang Shen、Mengting Liu、Hu Zhou、Xuyu Wang、Lulu Li、Aihua Yuan、Heng Song

  DOI：10.1002/cssc.202101203

  日期：2021.8.23

  with nitroaromatics and boronic acids using highly efficient and recyclable catalysts remains a challenge. In this study, nanoporous MoO3 confined in silica serves as an efficient heterogeneous catalyst for C−N cross-coupling of nitroaromatics with aryl or alkyl boronic acids to deliver N-arylamines and with desirable multiple reusability. Experimental results suggest that silica not only heterogenizes

  使用高效且可回收的催化剂构建与硝基芳烃和硼酸的 CN 键仍然是一个挑战。在这项研究中，限制在二氧化硅中的纳米多孔 MoO 3作为一种有效的多相催化剂，用于硝基芳烃与芳基或烷基硼酸的 CN 交叉偶联，以提供N-芳基胺，并具有理想的多次重复使用性。实验结果表明，二氧化硅不仅使受限介孔微环境中的 Mo 物种异质化，而且显着缩短了反应诱导期并调节了目标产物的化学效率。形状良好的 MoO 3 @m−SiO 2与均相 Mo 催化剂、商业 Pd/C 或 MoO 3纳米粒子相比，该催化剂在产率和周转数方面表现出改进的催化性能。这种方法为有价值的生物活性分子的多相催化合成提供了一条新途径。
• Novel compounds
  申请人：Demont Hubert Emmanuel

  公开号：US20060211740A1

  公开（公告）日：2006-09-21

  The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.

  本发明涉及一种新型的羟乙基胺化合物，具有Asp2（β-分泌酶，BACE1或Memapsin）抑制活性，其制备过程，含有它们的组合物以及它们在治疗β-淀粉样蛋白水平或β-淀粉样蛋白沉积物增高的疾病，尤其是阿尔茨海默病中的应用。
• Bifunctional AKR1C3 Inhibitors/Androgen Receptor Modulators and Methods of Use Thereof
  申请人：The Trustees of The University of Pennsylvania

  公开号：US20140107085A1

  公开（公告）日：2014-04-17

  The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

  该发明包括含有选择性AKR1C3抑制剂的组合物。该发明还包括含有双功能AKR1C3抑制剂和选择性雄激素受体调节剂的组合物。该发明还包括使用该发明的组合物进行治疗的方法。
• Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US09271961B2

  公开（公告）日：2016-03-01

  The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

  本发明包括含有选择性AKR1C3抑制剂的组合物。本发明还包括含有双功能AKR1C3抑制剂和选择性雄激素受体调节剂的组合物。本发明还包括使用本发明中的组合物进行治疗的方法。
• Light-Promoted Low-Valent-Tungsten-Catalyzed Ambient Temperature Amination of Boronic Acids with Nitroaromatics
  作者：Heng Song、Yang Shen、Hu Zhou、Danli Ding、Fu Yang、Yemei Wang、Chen Xu、Xingwei Cai

  DOI：10.1021/acs.joc.2c00138

  日期：2022.4.15

  conditions, nitroaromatics smoothly undergo C–N coupling reactions with their boronic acid partners, delivering structurally diverse secondary amines in good yields (>50 examples, yields up to 96%). This methodology is both scalable and highly chemoselective and engages both aliphatic and aromatic boronic acid partners. The catalysis is initiated by the deoxygenation of nitroaromatics by a trans-[W(CO)4(PPh3)2]

  在温和的条件下触发与硝基芳烃和硼酸形成 C-N 键是非常可取的，因为大多数先前的工作都是在恶劣的条件下进行的，有时化学或区域选择性较差。在此，公开了一种能够使硼酸与硝基芳族化合物在环境温度下胺化的低价钨催化反应。随手可得的 W(CO) 6作为无外部光敏剂条件下的预催化剂，硝基芳烃与它们的硼酸伙伴顺利进行 C-N 偶联反应，以良好的产率（>50 个实例，产率高达 96%）提供结构多样的仲胺。该方法具有可扩展性和高度化学选择性，并涉及脂肪族和芳香族硼酸伙伴。催化通过反式-[W(CO) 4 (PPh 3 ) 2 ] (反式-W , PPh 3 = 三苯基膦)配合物对硝基芳烃的脱氧引发，该配合物通过配体置换原位形成。