3-(methyl-(2-methyl-6-(4-methylpiperazine-1-yl)pyrimidine-4-yl)amino)anilinocarboxylic acid 4-nitro phenyl ester hydrochloride | 1402747-92-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(methyl-(2-methyl-6-(4-methylpiperazine-1-yl)pyrimidine-4-yl)amino)anilinocarboxylic acid 4-nitro phenyl ester hydrochloride
• 英文别名: 3-(methyl(2-methyl-6-(4-methylpiperazine-1-yl)pyrimidin-4-yl)amino)anilinocarboxylic acid 4-nitrophenyl ester hydrochloride；3-(methyl(2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)amino)anilinocarboxylic acid 4-nitrophenyl ester hydrochloride；(4-nitrophenyl) N-[3-[methyl-[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]amino]phenyl]carbamate;hydrochloride
• CAS: 1402747-92-5
• 化学式: C₂₄H₂₇N₇O₄*ClH
• 分子量: 513.984
• InChiKey: PHZQPSZBGAHBKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-(methyl-(2-methyl-6-(4-methylpiperazine-1-yl)pyrimidine-4-yl)amino)anilinocarboxylic acid 4-nitro phenyl ester hydrochloride 、 2-氯-5-氨基三氟甲苯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以25%的产率得到1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(methyl(2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl)amino)phenyl)urea
  参考文献：
  名称：

  Identification of Type II Inhibitors Targeting BRAF Using Privileged Pharmacophores

  摘要：

  V‐RAF murine sarcoma viral oncogene homologue B1 (BRAF) is the most frequently mutated protein kinase in human cancers. The most common mutant BRAF V600E constitutively activates the RAS/RAF/MEK/ERK signaling pathway. BRAF has been validated as an important therapeutic target in human cancers. Phenylaminopyrimidine and unsymmetrical diaryl urea are two privileged pharmacophores in kinase inhibitor drug discovery. Herein, we describe the design of a novel hybrid pharmacophore, 4‐phenylaminopyrimidine urea, using the above two pharmacophores. A new series of compounds were in turn synthesized and evaluated to successfully identify selective inhibitors of BRAF and oncogenic BRAF V600E. Once daily oral dosing of lead compound 3 demonstrated sustained antitumor efficacy in A549 human non‐small‐cell lung cancer xenograft model. Molecular docking suggested that compound 3 might be a type II kinase inhibitor binding to the DFG‐out conformation of BRAF.

  DOI：

  10.1111/cbdd.12198
• 作为产物：
  描述：

  N-甲基哌嗪 在 铁粉 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 4.83h， 生成 3-(methyl-(2-methyl-6-(4-methylpiperazine-1-yl)pyrimidine-4-yl)amino)anilinocarboxylic acid 4-nitro phenyl ester hydrochloride
  参考文献：
  名称：

  Identification of Type II Inhibitors Targeting BRAF Using Privileged Pharmacophores

  摘要：

  V‐RAF murine sarcoma viral oncogene homologue B1 (BRAF) is the most frequently mutated protein kinase in human cancers. The most common mutant BRAF V600E constitutively activates the RAS/RAF/MEK/ERK signaling pathway. BRAF has been validated as an important therapeutic target in human cancers. Phenylaminopyrimidine and unsymmetrical diaryl urea are two privileged pharmacophores in kinase inhibitor drug discovery. Herein, we describe the design of a novel hybrid pharmacophore, 4‐phenylaminopyrimidine urea, using the above two pharmacophores. A new series of compounds were in turn synthesized and evaluated to successfully identify selective inhibitors of BRAF and oncogenic BRAF V600E. Once daily oral dosing of lead compound 3 demonstrated sustained antitumor efficacy in A549 human non‐small‐cell lung cancer xenograft model. Molecular docking suggested that compound 3 might be a type II kinase inhibitor binding to the DFG‐out conformation of BRAF.

  DOI：

  10.1111/cbdd.12198