| 1174132-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• CAS: 1174132-36-5
• 化学式: C₂HF₃O₂*C₁₀H₁₂Cl₂N₂O₂S
• 分子量: 409.213
• InChiKey: QYSSPDDIHXHRAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.57
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-methyl-4-(2-methyl-2H-pyrazol-3-yl)-quinolin-8-ol 、 、 三氟乙酸 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 水 、 乙腈 为溶剂， 反应 18.0h， 以37%的产率得到2-{5-chloro-4-[2-methyl-4-(2-methyl-2H-pyrazol-3-yl)-quinolin-8-yloxymethyl]-pyridine-3-sulfinyl}-N,N-dimethyl-acetamide trifluoroacetate
  参考文献：
  名称：

  Novel Small Molecule Bradykinin B₂ Receptor Antagonists

  摘要：

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

  DOI：

  10.1021/jm9002445
• 作为产物：
  描述：

  2-(5-chloro-4-chloromethyl-pyridin-3-ylsulfanyl)-N,N-dimethyl-acetamide 、 三氟乙酸 在 双氧水 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 反应 24.0h， 以7%的产率得到
  参考文献：
  名称：

  Novel Small Molecule Bradykinin B₂ Receptor Antagonists

  摘要：

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

  DOI：

  10.1021/jm9002445