3-[(2,6-bis(methyl)phenyl)amino]benzoic acid methyl ester | 579510-27-3

• 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: 3-[(2,6-bis(methyl)phenyl)amino]benzoic acid methyl ester
• 英文别名: Methyl 3-(2,6-dimethylanilino)benzoate
• CAS: 579510-27-3
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: HQGGFMLJKNZIDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 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-[(2,6-bis(methyl)phenyl)amino]benzoic acid methyl ester 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以80%的产率得到3-[(2,6-bis(methyl)phenyl)amino]benzoic acid
  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
• 作为产物：
  描述：

  3-溴苯甲酸甲酯 、 2,6-二甲基苯胺 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78%的产率得到3-[(2,6-bis(methyl)phenyl)amino]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

• Transition-metal-catalyzed carbon-nitrogen bond-forming methods using carbene ligands
  申请人：——

  公开号：US20040044250A1

  公开（公告）日：2004-03-04

  The present invention relates to a process for the preparation of N-aryl amine and N-aryl amide compounds. Generally, the process of the present invention involves reacting a compound having a primary or secondary amino or amido group with an arylating compound, in the presence of a weak base and a transition metal catalyst, under reaction conditions effective to form an N-aryl amine or N-aryl amide compound, the transition metal catalyst comprising a Group 8 metal, e.g., Ni, Pd, or Pt, and at least one carbene-containing ligand. Typically, the transition metal catalyst is formed in a preceding step from the conjugate acid form of the carbene ligand, a stoichiometric amount of a strong base, and a Group 8 metal atom or ion.

  本发明涉及一种制备N-芳基胺和N-芳基酰胺化合物的方法。一般来说，本发明的方法涉及在弱碱和过渡金属催化剂的存在下，将具有一级或二级氨基或酰胺基的化合物与芳基化合物反应，形成N-芳基胺或N-芳基酰胺化合物的反应条件有效。过渡金属催化剂包括第8族金属，例如Ni、Pd或Pt，以及至少一个含卡宾的配体。通常，过渡金属催化剂是在前一步中由卡宾配体的共轭酸形式、一定量的强碱和第8族金属原子或离子形成的。
• US6888029B2
  申请人：——

  公开号：US6888029B2

  公开（公告）日：2005-05-03
• [EN] TRANSITION-METAL-CATALYZED CARBON-NITROGEN BOND-FORMING METHODS USING CARBENE LIGANDS<br/>[FR] PROCEDES DE FORMATION DE LIAISON CARBONE-AZOTE CATALYSEE PAR UN METAL DE TRANSITION A L'AIDE DE LIGANDS CARBENES
  申请人：MASSACHUSETTS INST TECHNOLOGY

  公开号：WO2003066570A1

  公开（公告）日：2003-08-14

  The present invention relates to a process for the preparation of N-aryl amine and N- aryl amide compounds. Generally, the process of the present invention involves reacting a compound having a primary or secondary amino or amido group with an arylating compound, in the presence of a weak base and a transition metal catalyst, under reaction conditions effective to form an N-aryl amine or N-aryl amide compound, the transition metal catalyst comprising a Group 8 metal, e.g., Ni, Pd, or Pt, and at least one carbene-containing ligand. Typically, the transition metal catalyst is formed in a preceding step from the conjugate acid form of the carbene ligand, a stoichiometric amount of a strong base, and a Group 8 metal atom or ion.
• 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.