N-(4-chloro-3-(pyridin-3-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide | 1195072-48-0

• 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-chloro-3-(pyridin-3-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide
• 英文别名: N-(4-chloro-3-pyridin-3-ylphenyl)-2-methyl-6-(trifluoromethyl)pyridine-3-carboxamide
• CAS: 1195072-48-0
• 化学式: C₁₉H₁₃ClF₃N₃O
• 分子量: 391.78
• InChiKey: HPROOKGHPPHWTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(4-chloro-3-iodophenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide 、 3-吡啶硼酸频哪醇酯 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.15h， 生成 N-(4-chloro-3-(pyridin-3-yl)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide
  参考文献：
  名称：

  GDC-0449—A potent inhibitor of the hedgehog pathway

  摘要：

  SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.049

文献信息

• GDC-0449—A potent inhibitor of the hedgehog pathway
  作者：Kirk D. Robarge、Shirley A. Brunton、Georgette M. Castanedo、Yong Cui、Michael S. Dina、Richard Goldsmith、Stephen E. Gould、Oivin Guichert、Janet L. Gunzner、Jason Halladay、Wei Jia、Cyrus Khojasteh、Michael F.T. Koehler、Karen Kotkow、Hank La、Rebecca L. LaLonde、Kevin Lau、Leslie Lee、Derek Marshall、James C. Marsters、Lesley J. Murray、Changgeng Qian、Lee L. Rubin、Laurent Salphati、Mark S. Stanley、John H.A. Stibbard、Daniel P. Sutherlin、Savita Ubhayaker、Shumei Wang、Susan Wong、Minli Xie

  DOI：10.1016/j.bmcl.2009.08.049

  日期：2009.10

  SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC. (C) 2009 Elsevier Ltd. All rights reserved.