4-hydroxymethyl-1-naphthoic acid | 57322-46-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-hydroxymethyl-1-naphthoic acid
• 英文别名: 4-(Hydroxymethyl)-1-naphthoic acid；4-(hydroxymethyl)naphthalene-1-carboxylic acid
• CAS: 57322-46-0
• 化学式: C₁₂H₁₀O₃
• 分子量: 202.21
• InChiKey: KTPCEPWBURBLPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxymethyl-1-naphthoic acid 在 manganese(IV) oxide 、 硫酸 、 sodium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 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-(溴甲基)萘-1-甲腈 在 sodium hydroxide 作用下， 反应 120.0h， 以72%的产率得到4-hydroxymethyl-1-naphthoic acid
  参考文献：
  名称：

  苯乙酸和 3-苯丙酸的取代 1-萘基甲酯的光化学：自由基对、离子对和 Marcus 电子转移

  摘要：

  苯乙酸 (3a-k) 和 3-苯基丙酸 (5a-c) 酸的环取代 1-萘基甲酯已在甲醇溶剂中光解。这些反应的主要产物来自两个关键中间体，即 1-萘甲基自由基/酰氧基自由基对和 1-萘甲基阳离子/羧酸根阴离子对。在从酰氧基中失去二氧化碳后，自由基对导致形成笼内偶联产物 8a-k 和 10a-c。离子对导致甲基醚 6a-k 和羧酸 7 和 9

  DOI：

  10.1021/ja00059a012

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。
• 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。
• [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。
• Aminoethanol derivatives
  申请人：——

  公开号：US20040127574A1

  公开（公告）日：2004-07-01

  The present invention provides a pharmaceutical agent having cholesteryl ester transfer protein inhibitory action and useful as a blood lipid lowering agent and the like. The present invention relates to a compound represented by the formula 1 wherein Ar 1 is an aromatic ring group optionally having substituents, Ar 2 is an aromatic ring group having substituents, OR″ is an optionally protected hydroxyl group, R is an acyl group, R′ is a hydrogen atom or a hydrocarbon group optionally having substituents, or a salt thereof, and a pharmaceutical composition containing a compound of the formula (I) or a salt thereof or a prodrug thereof.

  本发明提供了一种具有胆固醇酯转移蛋白抑制作用的药物剂，可用作降低血脂等方面的药物。本发明涉及一种由式1表示的化合物，其中Ar1是一个带有取代基的芳香环基团，Ar2是一个带有取代基的芳香环基团，OR″是一个可选保护的羟基，R是一个酰基，R′是一个氢原子或一个可选带有取代基的碳氢基团，或其盐，以及含有式(I)的化合物或其盐或前药的药物组合物。
• Controlled Self‐Assembly of Discrete Amphiphilic Oligourethanes with a Cascade Self‐Immolative Motif
  作者：Jie Xu、Changzhu Lv、Qiangqiang Shi、Jialin Zhang、Ning Wang、Guoying Zhang、Jinming Hu、Shiyong Liu

  DOI：10.1002/anie.202306119

  日期：2023.8.14

  Discrete polymers offer an excellent platform for comprehending the interplay between precise chain structures, distinctive self‐assembly behavior, and functional applications, whereas the development of discrete polymers with self‐immolative properties remains scarce. Here, we modularly synthesize a library of discrete self‐immolative oligourethanes containing N‐naphthylcarbamate or N‐(3‐fluorophenyl)carbamate repeating units via iterative stepwise growth. These oligourethanes undergo not only cascade 1,6‐elimination depolymerizations via photo‐mediated removal of o‐nitrobenzyl carbamate triggers but also selective cleavage of benzyl‐O linkages under MS/MS conditions even without UV light irradiation. In aqueous media, these discrete oligourethanes self‐assemble into different morphologies such as flat nanosheets, nanofibers, and nanoribbons, depending on the chain lengths and backbone compositions, and further morphological transitions are observed upon thermal annealing.

  摘要 离散聚合物为理解精确的链结构、独特的自组装行为和功能应用之间的相互作用提供了一个极好的平台，而具有自惰性的离散聚合物的开发仍然很少。在这里，我们通过迭代逐步生长的方法，模块化合成了含有 N-萘基氨基甲酸酯或 N-（3-氟苯基）氨基甲酸酯重复单元的离散自褪色低聚氨基甲酸酯库。这些低聚氨基甲酸酯不仅会通过光介导的邻硝基氨基甲酸苄酯触发器的去除而发生级联 1,6- 消除解聚，而且在 MS/MS 条件下，即使没有紫外光照射，也会发生苄基-O 链接的选择性裂解。在水介质中，这些离散的低聚氨基甲酸乙酯会根据链长和骨架成分的不同自组装成不同的形态，如扁平纳米片、纳米纤维和纳米带。