2-(6-甲氧基苯并[d]异噁唑-3-基)乙酸甲酯 | 34173-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 中文名称: 2-(6-甲氧基苯并[d]异噁唑-3-基)乙酸甲酯
• 英文名称: methyl (6-methoxy-1,2-benzisoxazol-3-yl) acetate
• 英文别名: 6-Methoxy-1,2-benzisoxazole-3-methylacetate；(6-methoxy-benzo[d]isoxazol-3-yl)-acetic acid methyl ester；Methyl 2-(6-methoxybenzo[D]isoxazol-3-YL)acetate；methyl 2-(6-methoxy-1,2-benzoxazol-3-yl)acetate
• CAS: 34173-01-8
• 化学式: C₁₁H₁₁NO₄
• 分子量: 221.213
• InChiKey: RATLYQCPYGHOAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-(6-甲氧基苯并[d]异噁唑-3-基)乙酸甲酯 在 盐酸 、 叠氮磷酸二苯酯 、 水 、 三溴化硼 、 sodium hydride 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 41.5h， 生成 N-(1-{6-[(4-ethoxybenzyl)oxy]-1,2-benzisoxazol-3-yl}ethyl)acetamide
  参考文献：
  名称：

  EP2351743

  摘要：

  公开号：
• 作为产物：
  描述：

  甲醇 、 2-(6-甲氧基苯并[d]异噁唑-3-基)乙酸 在 硫酸 作用下， 反应 1.5h， 生成 2-(6-甲氧基苯并[d]异噁唑-3-基)乙酸甲酯
  参考文献：
  名称：

  1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation

  摘要：

  Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.

  DOI：

  10.1021/jm020581y

文献信息

• BICYCLIC COMPOUND
  申请人：Kamata Makoto

  公开号：US20120010247A1

  公开（公告）日：2012-01-12

  The present invention provides a compound having an ACC inhibitory action, which is useful as an agent for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供了一种具有ACC抑制作用的化合物，其可用作预防或治疗肥胖症、糖尿病、高血压、高脂血症、心衰、糖尿病并发症、代谢综合征、肌肉萎缩、癌症等的药物，并具有优越的疗效。本发明涉及一种由式(I)表示的化合物，其中每个符号如规范中所定义，或其盐。
• Bicyclic compound
  申请人：Kamata Makoto

  公开号：US08501804B2

  公开（公告）日：2013-08-06

  The present invention provides a compound having an ACC inhibitory action, which is useful as an agent for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  本发明提供一种具有ACC抑制作用的化合物，可用作预防或治疗肥胖症、糖尿病、高血压、高脂血症、心力衰竭、糖尿病并发症、代谢综合征、肌肉萎缩、癌症等的药物，并具有卓越的疗效。本发明涉及一种由式（I）表示的化合物，其中每个符号如规范中所定义，或其盐。
• Benzisoxazole and benzisothiazole analogs of auxin
  作者：Mario Giannella、Fulvio Gualtieri、Carlo Melchiorre

  DOI：10.1016/s0031-9422(00)94694-6

  日期：1971.3
• EP2351743
  申请人：——

  公开号：——

  公开（公告）日：——
• 1,2-Benzisoxazole Phosphorodiamidates as Novel Anticancer Prodrugs Requiring Bioreductive Activation
  作者：Monish Jain、Chul-Hoon Kwon

  DOI：10.1021/jm020581y

  日期：2003.12.1

  Several 1,2-benzisoxazole phosphorodiamidates have been designed as prodrugs of phosphoramide mustard requiring bioreductive activation. Enzymatic reduction of 1,2-benziosoxazole moiety is expected to result in the formation of imine intermediate due to the cleavage of the N-O bond. The imine should then be spontaneously hydrolyzed to a ketone metabolite, thereby facilitating base-catalyzed beta-elimination of cytotoxic phosphoramide mustard. As expected, the proposed prodrugs 4, 9, and 12 were at least 3-5-fold more potent cytotoxins than control compounds 5 and 15, which lack in the phosphoramide mustard group. Upon incubation with phenobarb-induced rat liver S-9 fraction, compounds 4, 9, and 12 underwent extensive NADPH-dependent metabolism with concomitant generation of alkylating activity under both hypoxic and oxic conditions. Corresponding ketone metabolites were detected for 9 and 15. NADPH-dependent bioreduction of 15 to its ketone metabolite 16 was located in the microsomal fraction and inhibited by SKF-525A and pCMBA. Compared with phenobarb-induced rat liver microsomal fraction, incubation of 15 with rat or human P450 reductase microsomes showed moderate generation of 16. Microsomal cytochrome P450 and/or P450 reductase appear to be involved in the reductive metabolism of 1,2-benzisoxazole moiety under hypoxic as well as oxic conditions.