4-[（2-甲氧基乙基）氨基]-3-硝基苯甲酸 | 284672-80-6

• 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: 4-[（2-甲氧基乙基）氨基]-3-硝基苯甲酸
• 英文名称: 4-[(2-methoxyethyl)amino]-3-nitrobenzoic acid
• 英文别名: 4-(2-methoxyethylamino)-3-nitrobenzoic acid
• CAS: 284672-80-6
• 化学式: C₁₀H₁₂N₂O₅
• mdl: MFCD02089281
• 分子量: 240.216
• InChiKey: RSCXWQLDHNTXQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-[（2-甲氧基乙基）氨基]-3-硝基苯甲酸 在 4-二甲氨基吡啶 、 sodium metabisulfite 、 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 8.67h， 生成 N-(dimethylsulfamoyl)-2-(9-ethyl-9H-carbazol-3-yl)-1-(2-methoxyethyl)-1H-benzimidazole-5-carboxamide
  参考文献：
  名称：

  Identification of a Benzimidazolecarboxylic Acid Derivative (BAY 1316957) as a Potent and Selective Human Prostaglandin E2 Receptor Subtype 4 (hEP4-R) Antagonist for the Treatment of Endometriosis

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.8b01862
• 作为产物：
  描述：

  4-氯-3-硝基苯甲酸乙酯 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 4-[（2-甲氧基乙基）氨基]-3-硝基苯甲酸
  参考文献：
  名称：

  Novel benzimidazole derivatives as EP4 ligands

  摘要：

  本发明涉及一种新型苯并咪唑衍生物，其通式为(I)，以及其制备方法和用于制备治疗与EP4受体相关的疾病和适应症的药物组合物的用途。

  公开号：

  US20160318905A1

文献信息

• [EN] BENZOTRIAZOLES AND METHODS OF PROPHYLAXIS OR TREATMENT OF METABOLIC-RELATED DISORDERS THEREOF<br/>[FR] BENZOTRIAZOLES ET PROCEDES DE PREVENTION OU DE TRAITEMENT DES TROUBLES METABOLIQUE
  申请人：ARENA PHARM INC

  公开号：WO2004041274A1

  公开（公告）日：2004-05-21

  The present invention relates to certain benzotriazole carboxylic acid or ester derivatives of Formula (I), pharmaceutically acceptable salts and solvates thereof, which exhibit useful pharmaceutical properties, for example, as agonists for the GPCR referred to as hRUP38. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the prophylaxis or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for the use of the compounds of the invention in combination with other active agents such as those belonging to the class of -glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers and the like.

  本发明涉及公式（I）的若干苯并三唑羧酸或酯衍生物，其药学上可接受的盐和溶剂化物，具有有用的药理特性，例如作为称为hRUP38的GPCR激动剂。本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物在预防或治疗代谢相关疾病，包括血脂异常、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、综合征X等方面的方法。此外，本发明还提供了将本发明化合物与属于-葡萄糖苷酶抑制剂、醛还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烷合成抑制剂、非酯类、LDL降解增强剂、血管紧张素转化酶（ACE）抑制剂、胰岛素分泌增强剂等类别的其他活性剂联合使用的方法。
• Novel benzimidazole derivatives as EP4 ligands
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160318905A1

  公开（公告）日：2016-11-03

  The present invention relates to novel benzimidazole derivatives of the general formula (I), to processes for their preparation and to their use for preparing pharmaceutical compositions for the treatment of disorders and indications associated with the EP4 receptor.

  本发明涉及一种新型苯并咪唑衍生物，其通式为(I)，以及其制备方法和用于制备治疗与EP4受体相关的疾病和适应症的药物组合物的用途。
• Benzotriazoles and methods of prophylaxis or treatment of metabolic-related disorders thereof
  申请人：Semple Graeme

  公开号：US20060122240A1

  公开（公告）日：2006-06-08

  The present invention relates to certain benzotriazole carboxylic acid or ester derivatives of Formula (I), pharmaceutically acceptable salts and solvates thereof, which exhibit useful pharmaceutical properties, for example, as agonists for the GPCR referred to as hRUP38. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the prophylaxis or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for the use of the compounds of the invention in combination with other active agents such as those belonging to the class of -glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers and the like.

  本发明涉及公式（I）的某些苯并三唑羧酸或酯衍生物，其药学上可接受的盐和溶剂，具有有用的药理特性，例如作为被称为hRUP38的GPCR的激动剂。本发明还提供了含有该发明化合物的制药组合物，以及使用该发明化合物和组合物在预防或治疗代谢相关疾病，包括脂质代谢异常、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、综合征X等方面的方法。此外，本发明还提供了将该发明化合物与属于-葡萄糖苷酶抑制剂、醛糖还原酶抑制剂、双胍类药物、HMG-CoA还原酶抑制剂、角鲨烷合成抑制剂、纤维酸类、低密度脂蛋白降解增强剂、血管紧张素转换酶（ACE）抑制剂、胰岛素分泌增强剂等类别的其他活性剂一起使用的方法。
• 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。
• Benzimidazole derivatives as EP4 ligands
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US10730856B2

  公开（公告）日：2020-08-04

  The present invention relates to novel benzimidazole derivatives of the general formula (I), to processes for their preparation and to their use for preparing pharmaceutical compositions for the treatment of disorders and indications associated with the EP4 receptor.

  本发明涉及通式（I）的新型苯并咪唑衍生物、其制备工艺及其用于制备治疗与 EP4 受体相关的疾病和适应症的药物组合物。