N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((1-ethylpiperidin-4-yl)methyl)picolinamide | 1401533-34-3

• 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-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((1-ethylpiperidin-4-yl)methyl)picolinamide
• CAS: 1401533-34-3
• 化学式: C₃₁H₄₀N₆O₅
• 分子量: 576.696
• InChiKey: GRKDZXQGGJQPHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.45
• 重原子数：
  42.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  138.69
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((1-ethylpiperidin-4-yl)methyl)picolinamide 在 盐酸 、 sodium cyanoborohydride 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 5.0h， 生成 N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((1-ethylpiperidin-4-yl)methyl)picolinamide
  参考文献：
  名称：

  Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases

  摘要：

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.

  DOI：

  10.1021/ml300214g
• 作为产物：
  描述：

  methyl 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)methyl)picolinate 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.17h， 生成 N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-((1-ethylpiperidin-4-yl)methyl)picolinamide
  参考文献：
  名称：

  Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases

  摘要：

  A series of potent, selective platelet-derived growth factor receptor-family kinase inhibitors was optimized starting from a globally selective lead molecule 4 through structural modifications aimed at improving the physiochemical and pharmacoldnetic properties, as exemplified by 18b. Further clearance reduction via per-methylation of the a-carbons of a solubilizing piperidine nitrogen resulted in advanced leads 22a and 22b. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of compound 22b (AC710) as a preclinical development candidate.

  DOI：

  10.1021/ml300214g