(S)-1-fluoro-7-(2-fluoropyridin-3-yl)-3-(6-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine | 1335499-70-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (S)-1-fluoro-7-(2-fluoropyridin-3-yl)-3-(6-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine
• 英文别名: (5S)-1-fluoro-7-(2-fluoro-3-pyridinyl)-3-(6-fluoro-3-pyridinyl)spiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazol]-2-amine；(4S)-1'-fluoro-7'-(2-fluoropyridin-3-yl)-3'-(6-fluoropyridin-3-yl)spiro[5H-1,3-oxazole-4,5'-chromeno[2,3-c]pyridine]-2-amine
• CAS: 1335499-70-1
• 化学式: C₂₄H₁₄F₃N₅O₂
• 分子量: 461.403
• InChiKey: PCZDHXCSCIKBGH-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  95.5
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-3-chloro-1-fluoro-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine 、 2-氟-5-吡啶硼酸 在 potassium phosphate 、 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (S)-1-fluoro-7-(2-fluoropyridin-3-yl)-3-(6-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine
  参考文献：
  名称：

  An Orally Available BACE1 Inhibitor That Affords Robust CNS Aβ Reduction without Cardiovascular Liabilities

  摘要：

  BACE1 inhibition to prevent A beta peptide formation is considered to be a potential route to a disease-modifying treatment for Alzheimer's disease. Previous efforts in our laboratory using a combined structure- and property-based approach have resulted in the identification of aminooxazoline xanthenes as potent BACE1 inhibitors. Herein, we report further optimization leading to the discovery of inhibitor 15 as an orally available and highly efficacious BACE1 inhibitor that robustly reduces CSF and brain A beta levels in both rats and nonhuman primates. In addition, compound 15 exhibited low activity on the hERG ion channel and was well tolerated in an integrated cardiovascular safety model.

  DOI：

  10.1021/ml500458t