4-(naphthalen-1-ylamino)benzoic acid | 64436-30-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(naphthalen-1-ylamino)benzoic acid
• 英文别名: 4-(1-naphthylamino)benzoic acid
• CAS: 64436-30-2
• 化学式: C₁₇H₁₃NO₂
• 分子量: 263.296
• InChiKey: QXTNRERVIYSJRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(naphthalen-1-ylamino)benzoic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Discovery of Potent and Selective Sirtuin 2 (SIRT2) Inhibitors Using a Fragment-Based Approach

  摘要：

  Sirtuin 2 (SIRT2) is one of the sirtuins, a family of NAD(+)-dependent deacetylases that act on a variety of histone and non-histone substrates. Accumulating biological functions and potential therapeutic applications have drawn interest in the discovery and development of SIRT2 inhibitors. Herein we report our discovery of novel SIRT2 inhibitors using a fragment-based approach. Inspired by the purported close binding proximity of suramin and nicotinamide, we prepared two sets of fragments, namely, the naphthylamide sulfonic acids and the naphthalene-benzamides and -nicotinamides. Biochemical evaluation of these two series provided structure-activity relationship (SAR) information, which led to the design of (5-benzamidonaphthalen-1/2-yloxy)nicotinamide derivatives. Among these inhibitors, one compound exhibited high anti-SIRT2 activity (48 nM) and excellent selectivity for SIRT2 over SIRT1 and SIRT3. In vitro, it also increased the acetylation level of a-tubulin, a well-established SIRT2 substrate, in both concentration- and time-dependent manners. Further kinetic studies revealed that this compound behaves as a competitive inhibitor against the peptide substrate and most likely as a noncompetitive inhibitor against NAD(+). Taken together, these results indicate that we have discovered a potent and selective SIRT2 inhibitor whose novel structure merits further exploration.

  DOI：

  10.1021/jm500777s
• 作为产物：
  描述：

  methyl 4-(naphthalen-1-ylamino)benzoate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 水 为溶剂， 生成 4-(naphthalen-1-ylamino)benzoic acid
  参考文献：
  名称：

  Discovery of Potent and Selective Sirtuin 2 (SIRT2) Inhibitors Using a Fragment-Based Approach

  摘要：

  Sirtuin 2 (SIRT2) is one of the sirtuins, a family of NAD(+)-dependent deacetylases that act on a variety of histone and non-histone substrates. Accumulating biological functions and potential therapeutic applications have drawn interest in the discovery and development of SIRT2 inhibitors. Herein we report our discovery of novel SIRT2 inhibitors using a fragment-based approach. Inspired by the purported close binding proximity of suramin and nicotinamide, we prepared two sets of fragments, namely, the naphthylamide sulfonic acids and the naphthalene-benzamides and -nicotinamides. Biochemical evaluation of these two series provided structure-activity relationship (SAR) information, which led to the design of (5-benzamidonaphthalen-1/2-yloxy)nicotinamide derivatives. Among these inhibitors, one compound exhibited high anti-SIRT2 activity (48 nM) and excellent selectivity for SIRT2 over SIRT1 and SIRT3. In vitro, it also increased the acetylation level of a-tubulin, a well-established SIRT2 substrate, in both concentration- and time-dependent manners. Further kinetic studies revealed that this compound behaves as a competitive inhibitor against the peptide substrate and most likely as a noncompetitive inhibitor against NAD(+). Taken together, these results indicate that we have discovered a potent and selective SIRT2 inhibitor whose novel structure merits further exploration.

  DOI：

  10.1021/jm500777s

文献信息

• Naphthyl Derivatives as Inhibitors of Beta-Amyloid Aggregation
  申请人：Minetti Patrizia

  公开号：US20080255232A1

  公开（公告）日：2008-10-16

  Compounds useful in the treatment of disorders characterized by deposits of amyloid aggregates are herein described together with pharmaceutical compounds containing the same. In particular the compounds of the present invention are those having the Formula (I) as reported below, where the radicals have the meaning indicated in the description.

  本文描述了用于治疗由淀粉样聚集物沉积所特征化的疾病的化合物，以及含有相同化合物的药物化合物。特别是，本发明的化合物是具有下面报告的式（I）的化合物，其中基团具有描述中所示的含义。
• QUINOLINE DERIVATIVES FOR MODULATING DNA METHYLATION
  申请人：Phiasivongsa Pasit

  公开号：US20090285772A1

  公开（公告）日：2009-11-19

  Quinoline derivatives, particularly 4-anilinoquinoline derivatives, are provided. Such quinoline derivatives can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position, for example via selective inhibition of DNA methyltransferase DNMT1. Methods for synthesizing numerous 4-anilinoquinoline derivatives and for modulating DNA methylation are provided. Also provided are methods for formulating and administering these compounds or compositions to treat conditions such as cancer and hematological disorders.

  提供了喹啉衍生物，特别是4-苯胺基喹啉衍生物。这样的喹啉衍生物可用于调节DNA甲基化，例如通过选择性抑制DNA甲基转移酶DNMT1，有效抑制C-5位置的胞嘧啶甲基化。提供了合成多种4-苯胺基喹啉衍生物和调节DNA甲基化的方法。还提供了制剂和给药这些化合物或组合物以治疗癌症和血液疾病的方法。
• WO2007/45593
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Structure–Activity Relationship of <i>N</i>-Arylnaphthylamine Derivatives as Amyloid Aggregation Inhibitors
  作者：Roberto Di Santo、Roberta Costi、Giuliana Cuzzucoli Crucitti、Luca Pescatori、Federica Rosi、Luigi Scipione、Diana Celona、Mario Vertechy、Orlando Ghirardi、Paola Piovesan、Mauro Marzi、Silvio Caccia、Giovanna Guiso、Fabrizio Giorgi、Patrizia Minetti

  DOI：10.1021/jm301105m

  日期：2012.10.11

  Dyes like CR are able to inhibit the aggregation of A beta fibrils. Thus, a screening of a series of dyes including ABBB (1) was performed. Its main component 2 tested in an in vitro assay (i.e., ThT assay) showed good potency at inhibiting fibrils association. Congeners 4-9 have been designed and synthesized as inhibitors of A beta aggregation. A nurnber of these newly synthesized compounds have been found to be active in the ThT assay with IC50 of 1-57.4 mu M. The most potent compound of this series, 4k, showed micromolar activity in this test. Another potent derivative 4q (IC50 = 5.6 mu M) rapidly crossed the blood-brain barrier, achieving whole brain concentrations higher than in plasma. So 4q could be developed to find novel potent antiaggregating beta A agents useful in Alzheimer disease as well as other neurological diseases characterized by deposits of amyloid aggregates.
• NAPHTHYL DERIVATIVES AS INHIBITORS OF BETA-AMYLOID AGGREGATION
  申请人：SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

  公开号：EP1937243A2

  公开（公告）日：2008-07-02