3-(4-formylbenzoylamino)propionic acid methyl ester | 307989-15-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(4-formylbenzoylamino)propionic acid methyl ester
• 英文别名: methyl 3-[(4-formylbenzoyl)amino]propionate；methyl 3-[(4-formylbenzoyl)amino]propanoate
• CAS: 307989-15-7
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: GYBHAJPZBZVOMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-formylbenzoylamino)propionic acid methyl ester 在 sodium hydroxide 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 原甲酸三乙酯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 53.0h， 生成 3-{4-[1-(4-cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)ureidomethyl]-benzoylamino}propionic acid
  参考文献：
  名称：

  New β-Alanine Derivatives Are Orally Available Glucagon Receptor Antagonists

  摘要：

  A weak human glucagon receptor antagonist with an IC50 of 7 mu M was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.

  DOI：

  10.1021/jm058026u
• 作为产物：
  描述：

  3-氨基丙酸甲酯盐酸盐 、 对醛基苯甲酸 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 作用下， 以 二氯甲烷 为溶剂， 生成 3-(4-formylbenzoylamino)propionic acid methyl ester
  参考文献：
  名称：

  [EN] GLUCAGON RECEPTOR ANTAGONISTS, PREPARATION AND THERAPEUTIC USES
  [FR] ANTAGONISTE DES RECEPTEURS DU GLUCAGON, PREPARATION ET UTILISATIONS THERAPEUTIQUES

  摘要：

  本发明公开了具有胰高血糖素受体拮抗剂或逆拮抗剂活性的化合物I的新化合物，或其药用可接受的盐，以及制备这些化合物的方法。在另一实施例中，本发明公开了包含化合物I的药物组合物，以及使用它们治疗糖尿病和其他与胰高血糖素相关的代谢性疾病等方法。

  公开号：

  WO2005123668A1

文献信息

• Glucagon antagonists/inverse agonists
  申请人：——

  公开号：US20030065031A1

  公开（公告）日：2003-04-03

  Novel compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism and obesity.

  新化合物，其作用是拮抗胰高血糖素对胰高血糖素受体的作用。由于它们对胰高血糖素受体的拮抗作用，这些化合物可能适用于治疗和/或预防任何疾病和紊乱，其中胰高血糖素拮抗作用是有益的，如高血糖症、1型糖尿病、2型糖尿病、脂质代谢紊乱和肥胖症。
• Novel glucagon antagonists
  申请人：——

  公开号：US20030236292A1

  公开（公告）日：2003-12-25

  Novel compounds that act to antagonize the action of the glucagon peptide hormone on the glucagon receptor. More particularly, it relates to glucagon antagonists or inverse agonists.

  这是一种新型化合物，可以拮抗胰高血糖素肽激素在胰高血糖素受体上的作用。更具体地说，它涉及到胰高血糖素拮抗剂或反向激动剂。
• Glucagon Receptor Antagonists, Preparation and Therapeutic Uses
  申请人：Conner Eugene Scott

  公开号：US20070249688A1

  公开（公告）日：2007-10-25

  The present invention discloses novel compounds of Formula I, or pharmaceutically acceptable salts thereof, which have glucagon receptor antagonist or inverse agonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using them to treat diabetic and other glucagon related metabolic disorders, and the like.

  本发明公开了化合物I式的新型化合物，或其药学上可接受的盐，其具有葡萄糖高素受体拮抗剂或反向激动剂活性，以及制备这些化合物的方法。在另一种实施方式中，本发明还公开了包括I式化合物的药物组合物，以及使用它们治疗糖尿病和其他与葡萄糖高素相关的代谢性疾病的方法等。
• Glucagon receptor antagonists, preparation and therapeutic uses
  申请人：Eli Lilly and Company

  公开号：US07816557B2

  公开（公告）日：2010-10-19

  The present invention discloses novel compounds of Formula I, or pharmaceutically acceptable salts thereof, which have glucagon receptor antagonist or inverse agonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using them to treat diabetic and other glucagon related metabolic disorders, and the like.

  本发明披露了I式新化合物或其药学上可接受的盐，具有胰高血糖素受体拮抗剂或反向激动剂活性，以及制备该类化合物的方法。在另一实施例中，本发明披露了包含I式化合物的药物组成物，以及使用它们治疗糖尿病和其他胰高血糖素相关代谢紊乱等方法。
• GLUCAGON RECEPTOR ANTAGONISTS, PREPARATION AND THERAPEUTIC USES
  申请人：CONNER Scott Eugene

  公开号：US20110124648A1

  公开（公告）日：2011-05-26

  The present invention discloses novel compounds of Formula I, or pharmaceutically acceptable salts thereof, which have glucagon receptor antagonist or inverse agonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using them to treat diabetic and other glucagon related metabolic disorders, and the like.

  本发明披露了式I的新型化合物或其药学上可接受的盐，其具有胰高血糖素受体拮抗剂或反向激动剂活性，以及制备这种化合物的方法。在另一种实施方式中，本发明还披露了包含式I化合物的药物组合物，以及使用它们治疗糖尿病和其他胰高血糖素相关代谢紊乱等疾病的方法。