3-[(3-甲氧基苯基)氨基]苯甲酸甲酯 | 1055974-87-2

• 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-[(3-甲氧基苯基)氨基]苯甲酸甲酯
• 英文名称: 3-[(3-methoxyphenyl)amino]benzoic acid methyl ester
• 英文别名: Methyl 3-(3-methoxyanilino)benzoate
• CAS: 1055974-87-2
• 化学式: C₁₅H₁₅NO₃
• 分子量: 257.289
• InChiKey: NKCCTUCNRTYUCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(3-甲氧基苯基)氨基]苯甲酸甲酯 在 三乙基硅烷 、 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-{2-[(3-hydroxymethylphenyl)(3-methoxyphenyl)amino]ethyl} acetamide
  参考文献：
  名称：

  N-(苯胺基乙基)酰胺褪黑素配体，具有改善的水溶性和代谢稳定性

  摘要：

  MT 2选择性褪黑激素受体配体 UCM765 ( N- (2-((3-甲氧基苯基)(苯基)氨基)乙基)乙酰胺)在啮齿动物中表现出令人感兴趣的睡眠诱导、镇痛和抗焦虑特性，但其水溶性较低，适度的代谢稳定性。为了克服这些限制，研究了不同的策略，包括修饰易代谢位点、引入亲水取代基和设计更基本的衍生物。通过实验评估了新化合物的热力学溶解度、微粒体稳定性和亲脂性，以及它们的 MT 1和 MT 2结合亲和力。在 UCM765 的苯环上引入间羟甲基取代基，并用N-甲基-N-苯基-氨基取代N, N-二苯基-氨基支架，产生了具有良好微粒体稳定性的高度可溶性化合物，并且受体结合亲和力。对受体晶体结构的对接研究为其结合亲和力提供了理论依据。大鼠的药代动力学特征突显了 N-甲基-N-苯基-氨基衍生物的血浆浓度较高，与其改善的微粒体稳定性一致，并使该化合物值得考虑进行进一步的药理学研究。

  DOI：

  10.1002/cmdc.202100405
• 作为产物：
  描述：

  3-溴苯甲酸甲酯 、 间氨基苯甲醚 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97%的产率得到3-[(3-甲氧基苯基)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

• 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。
• [EN] NOVEL MELATONERGIC LIGANDS AND USES THEREOF<br/>[FR] NOUVEAUX LIGANDS MÉLATONINERGIQUES ET LEURS UTILISATIONS
  申请人：[en]GOBBI, Gabriella

  公开号：WO2022259219A1

  公开（公告）日：2022-12-15

  The present invention relates to novel melatonin ligands capable of modulating the melatonin receptors, particularly the melatonin receptor subtype MT2. Moreover, these compounds have been shown to be effective in the treatment of diseases and disorders associated with MT2 activity such as sleep disorders, major depression disorder, mood disorders, anxiety disorders, autism spectrum disorder, cognitive disorders, dementia,metabolic diseases included diabetes Type 1 and type 2, circadian rhythms disorders, pain, acute pain, inflammatory pain, chronic pain, neuropathic pain.
• 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.
• <i>N</i> ‐(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability
  作者：Francesca Ferlenghi、Michele Mari、Gabriella Gobbi、Gian Marco Elisi、Marco Mor、Silvia Rivara、Federica Vacondio、Silvia Bartolucci、Annalida Bedini、Fabiola Fanini、Gilberto Spadoni

  DOI：10.1002/cmdc.202100405

  日期：2021.10.6

  liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT1 and MT2 binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with

  MT 2选择性褪黑激素受体配体 UCM765 ( N- (2-((3-甲氧基苯基)(苯基)氨基)乙基)乙酰胺)在啮齿动物中表现出令人感兴趣的睡眠诱导、镇痛和抗焦虑特性，但其水溶性较低，适度的代谢稳定性。为了克服这些限制，研究了不同的策略，包括修饰易代谢位点、引入亲水取代基和设计更基本的衍生物。通过实验评估了新化合物的热力学溶解度、微粒体稳定性和亲脂性，以及它们的 MT 1和 MT 2结合亲和力。在 UCM765 的苯环上引入间羟甲基取代基，并用N-甲基-N-苯基-氨基取代N, N-二苯基-氨基支架，产生了具有良好微粒体稳定性的高度可溶性化合物，并且受体结合亲和力。对受体晶体结构的对接研究为其结合亲和力提供了理论依据。大鼠的药代动力学特征突显了 N-甲基-N-苯基-氨基衍生物的血浆浓度较高，与其改善的微粒体稳定性一致，并使该化合物值得考虑进行进一步的药理学研究。