4-hydroxymethyl-1-naphthaldehyde | 219684-99-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-hydroxymethyl-1-naphthaldehyde
• 英文别名: 4-hydroxymethylnaphthaldehyde；4-(Hydroxymethyl)-1-naphthaldehyde；4-(hydroxymethyl)naphthalene-1-carbaldehyde
• CAS: 219684-99-8
• 化学式: C₁₂H₁₀O₂
• 分子量: 186.21
• InChiKey: TVTQYGWDKUCAMX-UHFFFAOYSA-N

物化性质

• 沸点：
  401.7±20.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-hydroxymethyl-1-naphthaldehyde 在 硫酸 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-(2-Methyl-propane-1-sulfonylmethyl)-naphthalene-1-carbaldehyde
  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：

  1-溴-4-(溴甲基)萘 在 咪唑 、 4-二甲氨基吡啶 、 正丁基锂 、 对甲苯磺酸 、 calcium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 43.58h， 生成 4-hydroxymethyl-1-naphthaldehyde
  参考文献：
  名称：

  Effects of Electronics, Aromaticity, and Solvent Polarity on the Rate of Azaquinone–Methide-Mediated Depolymerization of Aromatic Carbamate Oligomers

  摘要：

  This paper uses physical-organic studies on well-defined oligomers to establish design principles for creating aromatic poly(carbamates) that depolymerize from head-to-tail in low dielectric constant environments when exposed to specific applied signals. We show that either increasing electron density or decreasing the aromaticity of aromatic repeating units in poly(carbamates) increase the overall depolymerization rate. For example, a methoxybenzene-based repeating unit provides depolymerization rates that are 143X faster than oligomers that contain a benzene-based repeating unit. Furthermore, the rate of depolymerization in the methoxybenzene-based system is tolerant to low dielectric environments, whereas the benzene-based oligomers are not.

  DOI：

  10.1021/jo400105m

文献信息

• [EN] GLUCAGON ANTAGONISTS/INVERSE AGONISTS<br/>[FR] ANTAGONISTES/AGONISTES INVERSES DU GLUCAGON
  申请人：NOVO NORDISK AS

  公开号：WO1999001423A1

  公开（公告）日：1999-01-14

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

  非肽化合物包含一个中心肼基结构，并且其合成方法。这些化合物作用是拮抗胰高血糖素肽激素的作用。
• [EN] GLUCAGON ANTAGONISTS/INVERSE AGONISTS<br/>[FR] ANTAGONISTES DE GLUCAGON/AGONISTES INVERSES
  申请人：NOVO NORDISK AS

  公开号：WO2000039088A1

  公开（公告）日：2000-07-06

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

  非肽类化合物包括中心腙基团和其合成方法。这些化合物的作用是拮抗葡萄糖肽激素的作用。
• GLUCAGON ANTAGONISTS/INVERSE AGONISTS
  申请人：NOVO NORDISK A/S

  公开号：EP0994848A1

  公开（公告）日：2000-04-26
• US6613942B1
  申请人：——

  公开号：US6613942B1

  公开（公告）日：2003-09-02