3-[N-(4-tert-butylphenyl)amino]benzoic acid methyl ester | 1284180-29-5

• 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-[N-(4-tert-butylphenyl)amino]benzoic acid methyl ester
• 英文别名: 3-[(4-tert-butylphenyl)amino]benzoic acid methyl ester；3-[N-(4-tert-Butylphenyl)amino]benzoic acid methyl ester；methyl 3-(4-tert-butylanilino)benzoate
• CAS: 1284180-29-5
• 化学式: C₁₈H₂₁NO₂
• 分子量: 283.37
• InChiKey: UMQIRANYOJDFGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 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-tert-butylphenyl)amino]benzoic acid methyl ester 在 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以91%的产率得到3-[N-(4-tert-butylphenyl)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 、 4-叔丁基苯胺 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81%的产率得到3-[N-(4-tert-butylphenyl)amino]benzoic acid methyl ester
  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

文献信息

• 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。
• US9271961B2
  申请人：——

  公开号：US9271961B2

  公开（公告）日：2016-03-01
• [EN] BIFUNCTIONAL AKR1C3 INHIBITORS/ANDROGEN RECEPTOR MODULATORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'AKR1C3 BIFONCTIONNELS/MODULATEURS DES RÉCEPTEURS AUX ANDROGÈNES, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV PENNSYLVANIA

  公开号：WO2012142208A1

  公开（公告）日：2012-10-18

  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.
• Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3)
  作者：Adegoke O. Adeniji、Barry M. Twenter、Michael C. Byrns、Yi Jin、Jeffrey D. Winkler、Trevor M. Penning

  DOI：10.1016/j.bmcl.2011.01.010

  日期：2011.3

  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.