2-(6-(2-(trifluoromethyl)phenyl)-2,6-diazaspiro[3.3]-heptanes-2-carboxamido)benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: 2-(6-(2-(trifluoromethyl)phenyl)-2,6-diazaspiro[3.3]-heptanes-2-carboxamido)benzoic acid
• 英文别名: 2-[[6-[2-(Trifluoromethyl)phenyl]-2,6-diazaspiro[3.3]heptane-2-carbonyl]amino]benzoic acid；2-[[6-[2-(trifluoromethyl)phenyl]-2,6-diazaspiro[3.3]heptane-2-carbonyl]amino]benzoic acid
• 化学式: C₂₀H₁₈F₃N₃O₃
• 分子量: 405.376
• InChiKey: GQZMIPOABTVFTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻溴三氟甲苯 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hydroxide monohydrate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 55.0h， 生成 2-(6-(2-(trifluoromethyl)phenyl)-2,6-diazaspiro[3.3]-heptanes-2-carboxamido)benzoic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Nonretinoid Retinol Binding Protein 4 Antagonists for the Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease

  摘要：

  Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-). mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

  DOI：

  10.1021/jm5010013