N-[(1S)-1-[(4-hydroxyphenyl)methyl]-2-oxo-2-(2-propylanilino)ethyl]-4-[(Z)-(4-oxo-2-thioxo-thiazolidin-5-ylidene)methyl]benzamide | 1352436-44-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[(1S)-1-[(4-hydroxyphenyl)methyl]-2-oxo-2-(2-propylanilino)ethyl]-4-[(Z)-(4-oxo-2-thioxo-thiazolidin-5-ylidene)methyl]benzamide
• 英文别名: N-[(2S)-3-(4-hydroxyphenyl)-1-oxo-1-(2-propylanilino)propan-2-yl]-4-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]benzamide
• CAS: 1352436-44-2
• 化学式: C₂₉H₂₇N₃O₄S₂
• 分子量: 545.683
• InChiKey: FUFBYVPUMKJSBV-FDJRJZQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 在 palladium 10% on activated carbon 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 环己烯 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-[(1S)-1-[(4-hydroxyphenyl)methyl]-2-oxo-2-(2-propylanilino)ethyl]-4-[(Z)-(4-oxo-2-thioxo-thiazolidin-5-ylidene)methyl]benzamide
  参考文献：
  名称：

  New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds

  摘要：

  We present a new class of inhibitors of pancreatic cholesterol esterase (CEase) based on 'priviledged' 5-benzylidenerhodanine and 5-benzylidene-2,4-thiazolidinedione structural scaffolds. The lead structures (5-benzylidenerhodanine 4a and 5-benzylidene-2,4-thiazolidinedione 4b) were identified in an in-house screening and these inhibited CEase with some selectivity over another serine hydrolase, acetylcholinesterase (AChE) (4a, CEase IC50 = 1.76 mu M vs AChE IC50 = 5.14 mu M and 4b, CEase IC50 = 5.89 mu M vs AChE IC50 > 100 mu M). A small library of analogs (5a-10a) containing a core amino acid in place of the glycerol group of the lead structures, was prepared to explore other potential binding interaction with CEase. These analogs inhibited CEase with IC50 values ranging from 1.44 to 85 mu M, with the majority exhibiting some selectivity for CEase versus AChE. The most potent compound of the library (10a) had 17-fold selectivity over AChE. We also report molecular docking (with CEase) and detailed kinetic analysis on the amino acid analogs to further understand the associated structure-activity relationships. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.042

文献信息

• New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds
  作者：Sabrina Heng、William Tieu、Stephanie Hautmann、Kevin Kuan、Daniel Sejer Pedersen、Markus Pietsch、Michael Gütschow、Andrew D. Abell

  DOI：10.1016/j.bmc.2011.10.042

  日期：2011.12

  We present a new class of inhibitors of pancreatic cholesterol esterase (CEase) based on 'priviledged' 5-benzylidenerhodanine and 5-benzylidene-2,4-thiazolidinedione structural scaffolds. The lead structures (5-benzylidenerhodanine 4a and 5-benzylidene-2,4-thiazolidinedione 4b) were identified in an in-house screening and these inhibited CEase with some selectivity over another serine hydrolase, acetylcholinesterase (AChE) (4a, CEase IC50 = 1.76 mu M vs AChE IC50 = 5.14 mu M and 4b, CEase IC50 = 5.89 mu M vs AChE IC50 > 100 mu M). A small library of analogs (5a-10a) containing a core amino acid in place of the glycerol group of the lead structures, was prepared to explore other potential binding interaction with CEase. These analogs inhibited CEase with IC50 values ranging from 1.44 to 85 mu M, with the majority exhibiting some selectivity for CEase versus AChE. The most potent compound of the library (10a) had 17-fold selectivity over AChE. We also report molecular docking (with CEase) and detailed kinetic analysis on the amino acid analogs to further understand the associated structure-activity relationships. (C) 2011 Elsevier Ltd. All rights reserved.