6-(1,1-dioxidothiomorpholin-4-yl)-4-[(2-fluoro-4-methylphenyl)amino]-7-methoxycinnoline-3-carboxamide | 1194373-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(1,1-dioxidothiomorpholin-4-yl)-4-[(2-fluoro-4-methylphenyl)amino]-7-methoxycinnoline-3-carboxamide
• 英文别名: 6-(1,1-Dioxo-1,4-thiazinan-4-yl)-4-(2-fluoro-4-methylanilino)-7-methoxycinnoline-3-carboxamide；6-(1,1-dioxo-1,4-thiazinan-4-yl)-4-(2-fluoro-4-methylanilino)-7-methoxycinnoline-3-carboxamide
• CAS: 1194373-71-1
• 化学式: C₂₁H₂₂FN₅O₄S
• 分子量: 459.501
• InChiKey: KWARCMYNKYVWMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-bromo-4-(2-fluoro-4-methylphenylamino)-7-methoxycinnoline-3-carbonitrile 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium hydroxide 作用下， 以 N,N-二甲基乙酰胺 、 叔丁醇 为溶剂， 生成 6-(1,1-dioxidothiomorpholin-4-yl)-4-[(2-fluoro-4-methylphenyl)amino]-7-methoxycinnoline-3-carboxamide
  参考文献：
  名称：

  Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507

  摘要：

  The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.031