2-chloro-6-(5-cyano-2-benzyloxyphenoxy)pyridine-4-carboxylic acid ethyl ester | 439801-32-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-6-(5-cyano-2-benzyloxyphenoxy)pyridine-4-carboxylic acid ethyl ester
• CAS: 439801-32-8
• 化学式: C₂₂H₁₇ClN₂O₄
• 分子量: 408.841
• InChiKey: KZDDGBBHFZYMPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.15
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  81.44
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-chloro-6-(5-cyano-2-benzyloxyphenoxy)pyridine-4-carboxylic acid ethyl ester 在 盐酸 、 potassium fluoride 、 氨 、 caesium carbonate 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 22.5h， 生成 2-(5-Carbamimidoyl-2-hydroxy-phenoxy)-6-[3-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-phenoxy]-isonicotinic acid
  参考文献：
  名称：

  Design, Synthesis, and Activity of a Novel Series of Factor Xa Inhibitors:  Optimization of Arylamidine Groups

  摘要：

  A novel series of diaryloxypyridines have been designed as selective nanomolar factor Xa (fXa) inhibitors for use as anticoagulants. In this paper, we describe our efforts to identify an additional interaction and a replacement for the distal amidine group that binds in the S3/S4 pocket of fXa. Introduction of a hydroxyl group para to the proximal amidine group increases the potency vs fXa by 1-2 orders of magnitude, which is the result of a hydrogen bond to Ser195 of the catalytic triad. A methyl imidazoline and a dimethylamide are good alternatives for the second amidine. These substitutions have increased the selectivity vs the related serine proteases trypsin and thrombin. The synthesis, in vitro activity, and hypothetical modes of binding to fXa based on trypsin crystallographic data are outlined.

  DOI：

  10.1021/jm0200660
• 作为产物：
  描述：

  2,6-二氯异烟酸乙酯 、 3-hydroxy-4-(benzyloxy)benzonitrile 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 以64%的产率得到2-chloro-6-(5-cyano-2-benzyloxyphenoxy)pyridine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Design, Synthesis, and Activity of a Novel Series of Factor Xa Inhibitors:  Optimization of Arylamidine Groups

  摘要：

  A novel series of diaryloxypyridines have been designed as selective nanomolar factor Xa (fXa) inhibitors for use as anticoagulants. In this paper, we describe our efforts to identify an additional interaction and a replacement for the distal amidine group that binds in the S3/S4 pocket of fXa. Introduction of a hydroxyl group para to the proximal amidine group increases the potency vs fXa by 1-2 orders of magnitude, which is the result of a hydrogen bond to Ser195 of the catalytic triad. A methyl imidazoline and a dimethylamide are good alternatives for the second amidine. These substitutions have increased the selectivity vs the related serine proteases trypsin and thrombin. The synthesis, in vitro activity, and hypothetical modes of binding to fXa based on trypsin crystallographic data are outlined.

  DOI：

  10.1021/jm0200660