trans-3-{4-[3-(2-bromo-4-trifluoromethoxyphenyl)-1-(tert-butylcyclohexyl)ureidomethyl]benzoylamino}propionic acid

• 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: trans-3-{4-[3-(2-bromo-4-trifluoromethoxyphenyl)-1-(tert-butylcyclohexyl)ureidomethyl]benzoylamino}propionic acid
• 英文别名: 3-{4-[3-(2-Bromo-4-trifluoromethoxyphenyl)-1-(trans-4-tert-butylcyclohexyl)ureidomethyl]-benzoylamino}propionic acid；3-{4-[3-(2-Bromo-4-trifluoromethoxyphenyl)-1-(trans-4-tert-butylcyclohexyl)ureidomethyl]benzoylamino}propionic Acid
• 化学式: C₂₉H₃₅BrF₃N₃O₅
• 分子量: 642.513
• InChiKey: JPGXZLNMGVIWFD-MEMLXQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.19
• 重原子数：
  41.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  107.97
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  对三氟甲氧基苯胺 在 sodium hydroxide 、 乙醇 、 溴 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.17h， 生成 trans-3-{4-[3-(2-bromo-4-trifluoromethoxyphenyl)-1-(tert-butylcyclohexyl)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

文献信息

• Glucagon antagonists/inverse agonists
  申请人：——

  公开号：US20030220350A1

  公开（公告）日：2003-11-27

  A novel class of 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 glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.

  一种新型化合物，可以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/或预防任何胰高血糖素介导的疾病和病症，如高血糖、1型糖尿病、2型糖尿病和肥胖症。
• Glucagon Antagonists/Inverse Agonists
  申请人：Lau Jesper

  公开号：US20090143592A1

  公开（公告）日：2009-06-04

  A novel class of 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 glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.

  一种新型化合物，可拮抗胰高血糖素对胰高血糖素受体的作用。由于这些化合物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/或预防任何胰高血糖素介导的疾病和病症，如高血糖、1型糖尿病、2型糖尿病和肥胖症。
• GLUCAGON ANTAGONISTS/INVERSE AGONISTS
  申请人：NOVO NORDISK A/S

  公开号：EP1183229B1

  公开（公告）日：2005-10-26
• US6503949B1
  申请人：——

  公开号：US6503949B1

  公开（公告）日：2003-01-07
• US6875760B2
  申请人：——

  公开号：US6875760B2

  公开（公告）日：2005-04-05