4-(3-Benzyloxy-propyl)-6-chloro-1,4-dihydro-benzo[d][1,3]oxazin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-(3-Benzyloxy-propyl)-6-chloro-1,4-dihydro-benzo[d][1,3]oxazin-2-one
• 英文别名: 6-Chloro-4-(3-phenylmethoxypropyl)-1,4-dihydro-3,1-benzoxazin-2-one
• 化学式: C₁₈H₁₈ClNO₃
• 分子量: 331.799
• InChiKey: AGXINYKJNNIDFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-苯基甲氧基-丁醛 、 4-氯-(N-Boc)苯胺 在 叔丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 以37%的产率得到[2-(4-Benzyloxy-1-hydroxy-butyl)-4-chloro-phenyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Efficient Syntheses of Benzothiazepines as Antagonists for the Mitochondrial Sodium−Calcium Exchanger:  Potential Therapeutics for Type II Diabetes

  摘要：

  Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.

  DOI：

  10.1021/jo020446t

文献信息

• Efficient Syntheses of Benzothiazepines as Antagonists for the Mitochondrial Sodium−Calcium Exchanger:  Potential Therapeutics for Type II Diabetes
  作者：Yazhong Pei、Michael J. Lilly、David J. Owen、Lawrence J. D'Souza、Xiao-Qing Tang、Jinghua Yu、Ramina Nazarbaghi、Andrew Hunter、Christen M. Anderson、Susan Glasco、Nicholas J. Ede、Ian W. James、Uday Maitra、S. Chandrasekaran、Walter H. Moos、Soumitra S. Ghosh

  DOI：10.1021/jo020446t

  日期：2003.1.1

  Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.