(5R)-5-(isocyanatomethyl)-2,2-dimethyl-1,3-dioxolan-4-one | 676547-12-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5R)-5-(isocyanatomethyl)-2,2-dimethyl-1,3-dioxolan-4-one
• CAS: 676547-12-9
• 化学式: C₇H₉NO₄
• 分子量: 171.153
• InChiKey: YPILCADZCWGCFJ-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  65
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5R)-5-(isocyanatomethyl)-2,2-dimethyl-1,3-dioxolan-4-one 、 苯甲醇 以 甲苯 为溶剂， 反应 17.0h， 以6.4 g的产率得到(R)-(2,2-dimethyl-5-oxo-[1,3]dioxalan-4-ylmethyl)carbamic acid benzyl 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：

  (R)-(-)-2,2-二甲基-5-氧-1,3-二氧戊环-4-乙酸 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 (5R)-5-(isocyanatomethyl)-2,2-dimethyl-1,3-dioxolan-4-one
  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