(+/-)-ethyl 3-azido-2-hydroxycyclopentanecarboxylate | 1821802-96-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (+/-)-ethyl 3-azido-2-hydroxycyclopentanecarboxylate
• 英文别名: Cyclopentanecarboxylic acid, 3-azido-2-hydroxy-, ethyl ester, (1S,2R,3S)-；ethyl (1S,2R,3S)-3-azido-2-hydroxycyclopentane-1-carboxylate
• CAS: 1821802-96-3
• 化学式: C₈H₁₃N₃O₃
• 分子量: 199.21
• InChiKey: GAMKLAYSHYGBDT-LYFYHCNISA-N

反应信息

• 作为反应物：
  描述：

  (+/-)-ethyl 3-azido-2-hydroxycyclopentanecarboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 生成 ethyl (1S,2R,3S)-3-amino-2-hydroxycyclopentane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of conformationally constrained glycerol 3-phosphate acyltransferase inhibitors

  摘要：

  Glycerol 3-phosphate acyltransferase (GPAT)isozymes are central control points for fat synthesis in mammals. Development of inhibitors of these membrane-bound enzymes could lead to an effective treatment for obesity, but is thwarted by an absence of direct structural information. Based on a highly successful study involving conformationally constrained glycerol 3-phosphate analogs functioning as potent glycerol 3-phosphate dehydrogenase inhibitors, several series of cyclic bisubstrate and transition state analogs were designed, synthesized, and tested as GPAT inhibitors. The weaker in vitro inhibitory activity of these compounds compared to a previously described benzoic acid series was then examined in docking experiments with the soluble squash chloroplast GPAT crystal structure. These in silico experiments indicate that cyclopentyl and cyclohexyl scaffolds prepared in this study may be occluded from the enzyme active site by two protein loops that sterically guard the phosphate binding region. In view of these findings, future GPAT inhibitor design will be driven toward compounds based on planar frameworks able to slide between these loops and enter the active site, resulting in improved inhibitory activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.091
• 作为产物：
  描述：

  (+/-)-ethyl 3-bromo-2-hydroxycyclopentanecarboxylate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (+/-)-ethyl 3-azido-2-hydroxycyclopentanecarboxylate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of conformationally constrained glycerol 3-phosphate acyltransferase inhibitors

  摘要：

  Glycerol 3-phosphate acyltransferase (GPAT)isozymes are central control points for fat synthesis in mammals. Development of inhibitors of these membrane-bound enzymes could lead to an effective treatment for obesity, but is thwarted by an absence of direct structural information. Based on a highly successful study involving conformationally constrained glycerol 3-phosphate analogs functioning as potent glycerol 3-phosphate dehydrogenase inhibitors, several series of cyclic bisubstrate and transition state analogs were designed, synthesized, and tested as GPAT inhibitors. The weaker in vitro inhibitory activity of these compounds compared to a previously described benzoic acid series was then examined in docking experiments with the soluble squash chloroplast GPAT crystal structure. These in silico experiments indicate that cyclopentyl and cyclohexyl scaffolds prepared in this study may be occluded from the enzyme active site by two protein loops that sterically guard the phosphate binding region. In view of these findings, future GPAT inhibitor design will be driven toward compounds based on planar frameworks able to slide between these loops and enter the active site, resulting in improved inhibitory activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.091