N³-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine | 700806-23-1

• 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: N³-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine
• 英文别名: n3-(3,4-Dimethoxy-phenyl)-1h-[1,2,4]triazole-3,5-diamine；3-N-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine
• CAS: 700806-23-1
• 化学式: C₁₀H₁₃N₅O₂
• 分子量: 235.246
• InChiKey: DIXFPLVSWYWDBR-UHFFFAOYSA-N

物化性质

• 沸点：
  464.5±55.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N³-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine 、 3,4,5-三甲氧基苯甲酰氯 在 吡啶 作用下， 以51%的产率得到(3-(3,4-dimethoxyphenylamino)-5-amino-1H-1,2,4-triazol-1-yl)-(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Synthesis, Antimitotic and Antivascular Activity of 1-(3′,4′,5′-Trimethoxybenzoyl)-3-arylamino-5-amino-1,2,4-triazoles

  摘要：

  A new class of compounds that incorporated the structural motif of the 1-(3',4',5'-trimethoxtbenzoyl)-3-arylamino-5-amino-1,2,4-triazole molecular skeleton was synthesized and evaluated for their antiproliferative activity in vitro, interactions with tubulin, and cell cycle effects. The most active agent, 3c, was evaluated for antitumor activity in vivo. Structure-activity relationships were elucidated with various substituents on the phenyl ring of the anilino moiety at the C-3 position of the 1,2,4-triazole ring. The best results for inhibition of cancer cell growth were obtained with the p-Me, m,p-diMe, and p-Et phenyl derivatives 3c, 3e, and 3f, respectively, and overall, these compounds were more or less as active as CA-4. Their vascular disrupting activity was evaluated in HUVEC cells, with compound 3c showing activity comparable with that of CA-4. Compound 3c almost eliminated the growth of syngeneic hepatocellular carcinoma in Balb/c mice, suggesting that 3c could be a new antimitotic agent with clinical potential.

  DOI：

  10.1021/jm5008193
• 作为产物：
  描述：

  3,4-二甲氧基苯基异硫氰酸酯 在 sodium hydroxide 、 溶剂黄146 、 三乙胺 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.5h， 生成 N³-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-3,5-diamine
  参考文献：
  名称：

  Highly Potent Inhibitors of Methionine Aminopeptidase-2 Based on a 1,2,4-Triazole Pharmacophore

  摘要：

  High-throughput screening for inhibitors of the human metalloprotease, methionine aminopeptidase-2 (MetAP2), identified a potent class of 3-anilino-5-benzylthio-1,2,4-triazole compounds. Efficient array and interative synthesis of triazoles led to rapid SAR development around the aniline, benzylthio, and triazole moeities. Evaluation of these analogs in a human MetAP2 enzyme assay led to the identification of several inhibitors with potencies in the 50-100 picomolar range. The deleterious effects on inhibitor potency by methylation of the anilino-triazole nitrogens, as well as the X-ray crystal structure of triazole 102 bound in the active site of MetAP2, confirm the key interactions between the triazole nitrogens, the active site cobalt atoms, and the His-231 side-chain. The structure has also provided a rationale for interpreting SAR within the triazole series. Key aniline (2-isopropylphenyl) and sulfur substituents (furanylmethyl) identified in the SAR studies led to the identification of potent inhibitors (103 and 104) of endothelial cell proliferation. Triazoles 103 and 104 also exhibited dose-dependent activity in an aortic ring tissue model of angiogenesis highlighting the potential utility of MetAP2 inhibitors as anticancer agents.

  DOI：

  10.1021/jm061182w

文献信息

• DIAMINOTRIAZOLES USEFUL AS INHIBITORS OF PROTEIN KINASES
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1562589B1

  公开（公告）日：2009-01-07