methyl 3-[(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)methyl]benzoate | 402739-13-3

• 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: methyl 3-[(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)methyl]benzoate
• 英文别名: methyl 3-[(3,5-dimethyl-4-nitropyrazol-1-yl)methyl]benzoate
• CAS: 402739-13-3
• 化学式: C₁₄H₁₅N₃O₄
• mdl: MFCD02253855
• 分子量: 289.291
• InChiKey: YNIXBSCDXCAGRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-[(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)methyl]benzoate 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 氨 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N-(1-(3-carbamoylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-4-(phenoxymethyl)benzamide
  参考文献：
  名称：

  N-(1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides: Antiproliferative Activity and Effects on mTORC1 and Autophagy

  摘要：

  Guided by antiproliferative activity in MIA PaCa-2 cells, we have performed preliminary structure activity relationship studies on N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides. Two selected compounds showed submicromolar antiproliferative activity and good metabolic stability. Both compounds reduced mTORC1 activity and increased autophagy at the basal level. In addition, they disrupted autophagic flux by interfering with mTORC1 reactivation and clearance of LC3-II under starvation/refeed conditions, as evidenced by accumulation of LC3-II and abnormal LC3 labeled punctae. Therefore, N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides may represent a new class of autophagy modulators that possesses potent anticancer activity and potentially a novel mechanism of action.

  DOI：

  10.1021/acsmedchemlett.6b00392
• 作为产物：
  描述：

  3,5-二甲基-4-硝基吡唑 、 3-(溴甲基)苯甲酸甲酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 3-[(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)methyl]benzoate
  参考文献：
  名称：

  N-(1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides: Antiproliferative Activity and Effects on mTORC1 and Autophagy

  摘要：

  Guided by antiproliferative activity in MIA PaCa-2 cells, we have performed preliminary structure activity relationship studies on N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides. Two selected compounds showed submicromolar antiproliferative activity and good metabolic stability. Both compounds reduced mTORC1 activity and increased autophagy at the basal level. In addition, they disrupted autophagic flux by interfering with mTORC1 reactivation and clearance of LC3-II under starvation/refeed conditions, as evidenced by accumulation of LC3-II and abnormal LC3 labeled punctae. Therefore, N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides may represent a new class of autophagy modulators that possesses potent anticancer activity and potentially a novel mechanism of action.

  DOI：

  10.1021/acsmedchemlett.6b00392