N-[4-(2-oxo-2-piperidin-1-ylethyl)-1,3-thiazol-2-yl]naphthalene-2-sulfonamide | 1577214-88-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[4-(2-oxo-2-piperidin-1-ylethyl)-1,3-thiazol-2-yl]naphthalene-2-sulfonamide
• CAS: 1577214-88-0
• 化学式: C₂₀H₂₁N₃O₃S₂
• 分子量: 415.537
• InChiKey: ATNKDWPAPYZMPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸乙酯 在 4-二甲氨基吡啶 、 aluminum (III) chloride 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 168.5h， 生成 N-[4-(2-oxo-2-piperidin-1-ylethyl)-1,3-thiazol-2-yl]naphthalene-2-sulfonamide
  参考文献：
  名称：

  Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl} acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antidiabetic activities

  摘要：

  Compounds 1-10 were designed using a bioisosteric approach and were prepared using a short synthetic route. The in vitro inhibitory activity of the compounds against 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) was evaluated. Compounds 5 (alpha-series) and 10 (beta-series) had a moderate inhibitory enzyme activity (55.26% and 67.03% inhibition at 10 mu M, respectively) and were as active as BVT.14225 (positive control). Both compounds have a piperidine ring in their structure, but the most active (10) was selected to establish its in vivo antidiabetic effect using a non insulin-dependent diabetes mellitus rat model. The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose in an acute model, and also by short term sub-chronic administration for 5 days. The results indicated a significant decrease of plasma glucose levels, similar than BVT.14225. Additionally, a molecular docking of the most active compounds of each series into the ligand binding pocket of one subunit of human 11 beta-HSD1 was performed. In this model the oxygen atom of the sulfonamide make hydrogen bond interactions with the catalytic residues Ser170 and Ala172. We also observed important pi-pi interactions between the naphthyl group and Tyr177. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.042

文献信息

• Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl} acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antidiabetic activities
  作者：Gabriel Navarrete-Vázquez、Maria Guadalupe Morales-Vilchis、Samuel Estrada-Soto、Juan José Ramírez-Espinosa、Sergio Hidalgo-Figueroa、Carlos Nava-Zuazo、Hugo Tlahuext、Ismael Leon-Rivera、José L. Medina-Franco、Fabian López-Vallejo、Scott P. Webster、Margaret Binnie、Rolffy Ortiz-Andrade、Hermenegilda Moreno-Diaz

  DOI：10.1016/j.ejmech.2013.12.042

  日期：2014.3

  Compounds 1-10 were designed using a bioisosteric approach and were prepared using a short synthetic route. The in vitro inhibitory activity of the compounds against 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) was evaluated. Compounds 5 (alpha-series) and 10 (beta-series) had a moderate inhibitory enzyme activity (55.26% and 67.03% inhibition at 10 mu M, respectively) and were as active as BVT.14225 (positive control). Both compounds have a piperidine ring in their structure, but the most active (10) was selected to establish its in vivo antidiabetic effect using a non insulin-dependent diabetes mellitus rat model. The antidiabetic activity of compound 10 was determined at 50 mg/kg single dose in an acute model, and also by short term sub-chronic administration for 5 days. The results indicated a significant decrease of plasma glucose levels, similar than BVT.14225. Additionally, a molecular docking of the most active compounds of each series into the ligand binding pocket of one subunit of human 11 beta-HSD1 was performed. In this model the oxygen atom of the sulfonamide make hydrogen bond interactions with the catalytic residues Ser170 and Ala172. We also observed important pi-pi interactions between the naphthyl group and Tyr177. (C) 2014 Elsevier Masson SAS. All rights reserved.