ethyl 4-(isopropylamino)-3-nitrobenzoate

• 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: ethyl 4-(isopropylamino)-3-nitrobenzoate
• 英文别名: ethyl 3-nitro-4-(propan-2-ylamino)benzoate
• 化学式: C₁₂H₁₆N₂O₄
• 分子量: 252.27
• InChiKey: CVFXPNIJPTXGHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 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：

  ethyl 4-(isopropylamino)-3-nitrobenzoate 在 sodium dithionite 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 以92%的产率得到3-氨基-4-(异丙基氨基)苯甲酸乙酯
  参考文献：
  名称：

  NovelN-Acylated Benzimidazolone Derivatives: Synthesis, 2D-QSAR and Targets Prediction

  摘要：

  A series of novel N-acylated benzimidazolone derivatives, were synthesized from 4-aminobenzoic acid, and their antifungal activities against Botrytis cinerea were evaluated by spore germination assay. Preliminary results indicated that most of the benzimidazolone derivatives had inhibitory effect on spore germination, among which 6-carboxylate substituted derivatives were more effective than its 5-substituted regioisomers. Furthermore, 2D-quantitative structure-activity relationship (2D-QSAR) studies revealed good predictive and statistically significant QSAR models, as well as highlighted that the activities were strongly influenced by the type of introduced acyl groups in the benzimidazolone moiety. Potential targets of the title compounds were predicted using ligand profiling and validated by molecular docking, and the results implied that the title compounds might be a new type of fatty acid synthetase inhibitor.

  DOI：

  10.5935/0103-5053.20150019
• 作为产物：
  描述：

  4-氨基-3-硝基苯甲酸乙酯 、 丙酮 在 sodium tetrahydroborate 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以86%的产率得到ethyl 4-(isopropylamino)-3-nitrobenzoate
  参考文献：
  名称：

  NovelN-Acylated Benzimidazolone Derivatives: Synthesis, 2D-QSAR and Targets Prediction

  摘要：

  A series of novel N-acylated benzimidazolone derivatives, were synthesized from 4-aminobenzoic acid, and their antifungal activities against Botrytis cinerea were evaluated by spore germination assay. Preliminary results indicated that most of the benzimidazolone derivatives had inhibitory effect on spore germination, among which 6-carboxylate substituted derivatives were more effective than its 5-substituted regioisomers. Furthermore, 2D-quantitative structure-activity relationship (2D-QSAR) studies revealed good predictive and statistically significant QSAR models, as well as highlighted that the activities were strongly influenced by the type of introduced acyl groups in the benzimidazolone moiety. Potential targets of the title compounds were predicted using ligand profiling and validated by molecular docking, and the results implied that the title compounds might be a new type of fatty acid synthetase inhibitor.

  DOI：

  10.5935/0103-5053.20150019

文献信息

• NOVEL BENZIMIDAZOLE DERIVATIVES AS EP4 ANTAGONISTS
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160214977A1

  公开（公告）日：2016-07-28

  The present invention relates to novel benzimidazole derivatives of the general formula (I), processes for their preparation and their use for the production of pharmaceutical compositions for the treatment of diseases and indications that are connected with the receptor EP4.

  本发明涉及通式(I)的新型苯并咪唑衍生物，其制备方法以及它们用于制备治疗与EP4受体相关的疾病和适应症的药物组合物的用途。
• Identification of a Benzimidazolecarboxylic Acid Derivative (<b>BAY 1316957</b>) as a Potent and Selective Human Prostaglandin E2 Receptor Subtype 4 (hEP4-R) Antagonist for the Treatment of Endometriosis
  作者：Stefan Bäurle、Jens Nagel、Olaf Peters、Nico Bräuer、Antonius ter Laak、Cornelia Preusse、Antje Rottmann、Dieter Heldmann、Ulrich Bothe、Thorsten Blume、Ludwig Zorn、Daryl Walter、Thomas M. Zollner、Andreas Steinmeyer、Gernot Langer

  DOI：10.1021/acs.jmedchem.8b01862

  日期：2019.3.14

  The presence and growth of endometrial tissue outside the uterine cavity in endometriosis patients are primarily driven by hormone-dependent and inflammatory processes-the latter being frequently associated with severe, acute, and chronic pelvic pain. The EP4 subtype of prostaglandin E2 (PGE2) receptors (EP4-R) is a particularly promising antiinflammatory and antinociceptive target as both this receptor subtype and the pathways forming PGE2 are highly expressed in endometriotic lesions. High-throughput screening resulted in the identification of benzimidazole derivatives as novel hEP4-R antagonists. Careful structure-activity relationship investigation guided by rational design identified a methyl substitution adjacent to the carboxylic acid as an appropriate means to accomplish favorable pharmacokinetic properties by reduction of glucuronidation. Further optimization led to the identification of benzimidazolecarboxylic acid BAY 1316957, a highly potent, specific, and selective hEP4-R antagonist with excellent drug metabolism and pharmacokinetics properties. Notably, treatment with BAY 1316957 can be expected to lead to prominent and rapid pain relief and significant improvement of the patient's quality of life.
• NEUARTIGE BENZIMIDAZOLDERIVATE ALS EP4-ANTAGONISTEN
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP2928884A1

  公开（公告）日：2015-10-14
• US9708311B2
  申请人：——

  公开号：US9708311B2

  公开（公告）日：2017-07-18
• [EN] SUBSTITUTED BENZIMIDAZOLES AS CANNABINOID MODULATOR<br/>[FR] BENZIMIDAZOLES SUBSTITUÉS EN TANT QUE MODULATEUR CANNABINOÏDE
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2009116074A2

  公开（公告）日：2009-09-24

  The present invention relates to novel compounds of general formula (I), their stereoisomers, regioisomers, tautomeric forms and novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them. The present invention also relates to a process of preparing novel compounds of general formula (I), their stereoisomers, regioisomers, their tautomeric forms, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutical compositions containing them, and novel intermediates involved in their synthesis.