3-tert-butoxycarbonylamino-2(R)-methoxypropionic acid methyl ester | 385837-06-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-tert-butoxycarbonylamino-2(R)-methoxypropionic acid methyl ester
• 英文别名: (R)-Methyl 3-((tert-butoxycarbonyl)amino)-2-methoxypropanoate；methyl (2R)-2-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 385837-06-9
• 化学式: C₁₀H₁₉NO₅
• 分子量: 233.265
• InChiKey: YWQFAROVRDNBOM-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-tert-butoxycarbonylamino-2(R)-methoxypropionic acid methyl ester 在 三氟乙酸 、 盐酸 作用下， 以 二氯甲烷 、 乙醚 为溶剂， 反应 0.5h， 以88%的产率得到3-amino-2(R)-methoxypropionic acid methyl ester
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599
• 作为产物：
  描述：

  、 叔丁醇 以 甲苯 为溶剂， 反应 16.0h， 以600 mg的产率得到3-tert-butoxycarbonylamino-2(R)-methoxypropionic acid methyl ester
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599

文献信息

• Glucagon antagonists/inverse agonists
  申请人：——

  公开号：US20020143186A1

  公开（公告）日：2002-10-03

  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 diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism, such as dyslipidemia, and obesity.

  一种新型化合物类别，其作用是拮抗胰高血糖素激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拮抗作用有益的疾病和疾病，如高血糖症、1型糖尿病、2型糖尿病、脂质代谢紊乱疾病，如血脂异常和肥胖症。
• US6562807B2
  申请人：——

  公开号：US6562807B2

  公开（公告）日：2003-05-13
• US6953812B2
  申请人：——

  公开号：US6953812B2

  公开（公告）日：2005-10-11
• Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor
  作者：János T. Kodra、Anker Steen Jørgensen、Birgitte Andersen、Carsten Behrens、Christian Lehn Brand、Inger Thøger Christensen、Mette Guldbrandt、Claus Bekker Jeppesen、Lotte B. Knudsen、Peter Madsen、Erica Nishimura、Christian Sams、Ulla G. Sidelmann、Raymon A. Pedersen、Francis C. Lynn、Jesper Lau

  DOI：10.1021/jm7015599

  日期：2008.9.11

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.