3-(4-methyl-anilino)-5-(5-methyl-isoxazol-3-ylmethylthio)-1,2,4-triazole | 334538-93-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 3-(4-methyl-anilino)-5-(5-methyl-isoxazol-3-ylmethylthio)-1,2,4-triazole
• 英文别名: 3-[(5-methyl-1,2-oxazol-3-yl)methylsulfanyl]-N-(4-methylphenyl)-1H-1,2,4-triazol-5-amine
• CAS: 334538-93-1
• 化学式: C₁₄H₁₅N₅OS
• 分子量: 301.372
• InChiKey: QWHUCUJGEQGJHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4-Dithio-1-(p-tolyl)biuret 在 potassium carbonate 、 溶剂黄146 、 三乙胺 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成 3-(4-methyl-anilino)-5-(5-methyl-isoxazol-3-ylmethylthio)-1,2,4-triazole
  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

• 1,2,4-triazole derivatives, compositions, process of making and methods of use
  申请人：Marino P. Joseph

  公开号：US20050267185A1

  公开（公告）日：2005-12-01

  Compounds of this invention are non-peptide, reversible inhibitors of type 2 methionine aminopeptidase, useful in treating conditions mediated by angiogenesis, such as cancer, haemangioma, proliferative retinopathy, rheumatoid arthritis, atherosclerotic neovascularization, psoriasis, ocular neovascularization and obesity.

  本发明的化合物是非肽类、可逆抑制剂，用于治疗通过血管生成介导的疾病，如癌症、血管瘤、增生性视网膜病变、类风湿性关节炎、动脉粥样硬化新生血管形成、牛皮癣、眼部新生血管形成和肥胖症。
• COMPOUNDS AND METHODS
  申请人：SmithKline Beecham Corporation

  公开号：EP1223932A1

  公开（公告）日：2002-07-24
• EP1223932A4
  申请人：——

  公开号：EP1223932A4

  公开（公告）日：2003-01-15
• US7304082B2
  申请人：——

  公开号：US7304082B2

  公开（公告）日：2007-12-04
• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSES ET METHODES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001024796A1

  公开（公告）日：2001-04-12

  Compounds of this invention are non-peptide, reversible inhibitors of type 2 methionine aminopeptidase, useful in treating conditions mediated by angiogenesis, such as cancer, haemangioma, proliferative retinopathy, rheumatoid arthritis, atherosclerotic neovascularization, psoriasis, ocular neovascularization and obesity.