2-(naphthalen-2-yloxy)-N-tosylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(naphthalen-2-yloxy)-N-tosylacetamide
• 英文别名: N-(4-methylphenyl)sulfonyl-2-naphthalen-2-yloxyacetamide
• 化学式: C₁₉H₁₇NO₄S
• 分子量: 355.414
• InChiKey: VSMRSWRUYZRWGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2-萘氧基)乙酸甲酯 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 44.0h， 生成 2-(naphthalen-2-yloxy)-N-tosylacetamide
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators

  摘要：

  Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.

  DOI：

  10.1021/acs.jmedchem.9b02094

文献信息

• [EN] SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1<br/>[FR] ACTIVATEURS NUCLÉOTIDIQUES NON CYCLIQUES SÉLECTIFS POUR LE CAPTEUR DE CAMP EPAC 1
  申请人：UNIV TEXAS

  公开号：WO2021188728A9

  公开（公告）日：2022-08-11
• Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators
  作者：Pingyuan Wang、Urszula Luchowska-Stańska、Boy van Basten、Haiying Chen、Zhiqing Liu、Jolanta Wiejak、Padraic Whelan、David Morgan、Emma Lochhead、Graeme Barker、Holger Rehmann、Stephen J. Yarwood、Jia Zhou

  DOI：10.1021/acs.jmedchem.9b02094

  日期：2020.5.28

  Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.