2-(1,2-benzothiazol-3-ylamino)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-1,3-thiazol-4-one | 1027341-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(1,2-benzothiazol-3-ylamino)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-1,3-thiazol-4-one
• CAS: 1027341-19-0
• 化学式: C₁₈H₁₃N₃O₃S₂
• 分子量: 383.452
• InChiKey: MVMPYCDFQNONAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(benzo[d]isothiazol-3-ylimino)thiazolidin-4-one 、 香草醛 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 4.0h， 生成 2-(1,2-benzothiazol-3-ylamino)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-1,3-thiazol-4-one
  参考文献：
  名称：

  2-Thiazolylimino/Heteroarylimino-5-arylidene-4-thiazolidinones as New Agents with SHP-2 Inhibitory Action

  摘要：

  SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to continuously active enzyme were found in more than 50% of Noonan syndrome patients and are considered to be responsible for the high tendency of these patients to juvenile leukemias and other cancer types. Recently SHP-2 became a new drug target, but till flow little has been done in this field. In the present study, 172-thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones divided into three series of derivatives bearing thiazole-, benzo[d]thiazole-, and benzo[d]isothizole rings were tested for SHP-2 inhibitory activity. Most of the compounds were good SHP-2 inhibitors. Benzo[d]thiazole derivatives exhibited the best inhibitory action. Docking studies revealed that hydrophobic interactions and hydrogen bond formation stabilize enzyme-inhibitor complex.

  DOI：

  10.1021/jm8004306

文献信息

• 2-Thiazolylimino/Heteroarylimino-5-arylidene-4-thiazolidinones as New Agents with SHP-2 Inhibitory Action
  作者：A. Geronikaki、P. Eleftheriou、P. Vicini、I. Alam、A. Dixit、A. K. Saxena

  DOI：10.1021/jm8004306

  日期：2008.9.11

  SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to continuously active enzyme were found in more than 50% of Noonan syndrome patients and are considered to be responsible for the high tendency of these patients to juvenile leukemias and other cancer types. Recently SHP-2 became a new drug target, but till flow little has been done in this field. In the present study, 172-thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones divided into three series of derivatives bearing thiazole-, benzo[d]thiazole-, and benzo[d]isothizole rings were tested for SHP-2 inhibitory activity. Most of the compounds were good SHP-2 inhibitors. Benzo[d]thiazole derivatives exhibited the best inhibitory action. Docking studies revealed that hydrophobic interactions and hydrogen bond formation stabilize enzyme-inhibitor complex.