N-(3,5-dichloro-4-pyridyl)-2,3,4-trimethoxybenzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,5-dichloro-4-pyridyl)-2,3,4-trimethoxybenzamide
• 英文别名: N-(3,5-Dichloro-4-pyridinyl)-2,3,4-trimethoxybenzamide；N-(3,5-dichloropyridin-4-yl)-2,3,4-trimethoxybenzamide
• 化学式: C₁₅H₁₄Cl₂N₂O₄
• 分子量: 357.193
• InChiKey: UZPDIDQXBHSLFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3,4-三甲氧基苯甲酸 在 氯化亚砜 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 13.0h， 生成 N-(3,5-dichloro-4-pyridyl)-2,3,4-trimethoxybenzamide
  参考文献：
  名称：

  Discovery and Early Clinical Development of 2-{6-[2-(3,5-Dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide (LEO 29102), a Soft-Drug Inhibitor of Phosphodiesterase 4 for Topical Treatment of Atopic Dermatitis

  摘要：

  Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the dinic for PDE4 inhibitors, primarily due to PDE4 mediated side effects. Here we describe our approach to circumvent this issue by applying a soft-drug concept in the design of a topically acting PDE4 inhibitor for treatment of dermatological diseases. We used a fast follower approach, starting from piclamilast. In particular, simultaneous introduction of 2'-alkoxy substituents and changing an amide to a keto linker proved to be beneficial when designing potential soft-drug candidates. This effort culminated in identification of LEO 29102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-friendly formulations giving efficient drug delivery to the skin. Compound 20 has reached phase 2 and demonstrated clinically relevant efficacy in the treatment of atopic dermatitis.

  DOI：

  10.1021/jm500378a