4-甲酰基萘-1-羧酸 | 219685-15-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-甲酰基萘-1-羧酸
• 英文名称: 4-formylnaphthalene-1-carboxylic acid
• CAS: 219685-15-1
• 化学式: C₁₂H₈O₃
• 分子量: 200.194
• InChiKey: INKOQGZWHUTYIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲酰基萘-1-羧酸 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-甲酰基-萘-1-羧酸二乙基酰胺
  参考文献：
  名称：

  Optimization of Alkylidene Hydrazide Based Human Glucagon Receptor Antagonists. Discovery of the Highly Potent and Orally Available 3-Cyano-4-hydroxybenzoic Acid [1-(2,3,5,6-Tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide

  摘要：

  Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-eyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure-metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylenelhydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, K-B = 760 pM) and of the isolated rat receptor IC50 = 430 pM, K-B = 380 pM). Glucagon-stimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (K-i = 14 nM). This compound was orally available in dogs (F-po = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.

  DOI：

  10.1021/jm0208572
• 作为产物：
  描述：

  4-羟甲基-1-萘甲酸甲酯 在 manganese(IV) oxide 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 4-甲酰基萘-1-羧酸
  参考文献：
  名称：

  Optimization of Alkylidene Hydrazide Based Human Glucagon Receptor Antagonists. Discovery of the Highly Potent and Orally Available 3-Cyano-4-hydroxybenzoic Acid [1-(2,3,5,6-Tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide

  摘要：

  Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-eyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure-metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylenelhydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, K-B = 760 pM) and of the isolated rat receptor IC50 = 430 pM, K-B = 380 pM). Glucagon-stimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (K-i = 14 nM). This compound was orally available in dogs (F-po = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.

  DOI：

  10.1021/jm0208572

文献信息

• Glucagon antagonists/inverse agonists
  申请人：Novo Nordisk A/S

  公开号：US06613942B1

  公开（公告）日：2003-09-02

  Non-peptide compounds comprising a central hydrazide motif and methods for the synthesis thereof are disclosed. The compounds act to antagonize the action of the glucagon peptide hormone.

  本发明公开了包含中央腙基结构的非肽化合物及其合成方法。这些化合物具有拮抗胰高血糖素肽激素作用的作用。
• [EN] ISOXAZOLINE DERIVATIVES AS PESTICIDES<br/>[FR] DÉRIVÉS D'ISOXAZOLINE EN TANT QUE PESTICIDES
  申请人：ELANCO TIERGESUNDHEIT AG

  公开号：WO2021127188A1

  公开（公告）日：2021-06-24

  The present invention provides compounds of formula (I): which are useful for long-lasting treatment and control of pests, for example fleas and ticks, in companion animals and livestock, and pharmaceutical compositions and methods of using the same.

  本发明提供了公式（I）的化合物，这些化合物对于伴侣动物和牲畜中的害虫，例如跳蚤和蜱的长效治疗和控制非常有用，还提供了药物组合物和使用方法。
• 一种制备噁唑啉杀虫剂阿福拉纳中间体的方法
  申请人：丽珠集团新北江制药股份有限公司

  公开号：CN112679338A

  公开（公告）日：2021-04-20

  本发明公开了一种制备噁唑啉杀虫剂阿福拉纳中间体的方法，该中间体为4‑甲酰基‑萘‑1‑羧酸，与US6613942B1的合成路线相比。本发明一些实例的方法，通过探索，将反应步骤由3步缩短到1步，不仅可以得到纯度合格的噁唑啉杀虫剂阿福拉纳中间体产品。在简化了中间体控制步骤的同时，提高了产品收率，更加易于工业化生产。
• 一种制备异噁唑啉类中间体及异噁唑啉的方 法
  申请人：丽珠集团新北江制药股份有限公司

  公开号：CN110028462B

  公开（公告）日：2021-03-23

  本发明公开了一种制备异噁唑啉类中间体及异噁唑啉的方法，中间体的制备包括使用为起始原料，经羟胺肟化反应，之后与N‑卤代琥珀酰亚胺进行取代反应，消除&环合得到异噁唑啉类中间体。该方法反应条件温和，制得的异噁唑啉中间体杂质含量少。
• 一种异噁唑啉类杀虫剂的制备方法
  申请人：丽珠集团新北江制药股份有限公司

  公开号：CN109879826B

  公开（公告）日：2021-04-13

  本发明公开了一种异噁唑啉类杀虫剂的制备方法，包括以为起始原料，经肟化和酰胺缩合得到进一步与NXS取代，消除、环化得到异噁唑啉类杀虫剂。本方法在降低中间体纯化的难度同时，也降低了产品纯化的难度，从而提高了产品质量和收率，最终提高了产品的竞争力。