N'-[(2-hydroxynaphthalen-1-yl)methylene]-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbohydrazone | 329789-76-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N'-[(2-hydroxynaphthalen-1-yl)methylene]-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbohydrazone
• 英文别名: N-[(2-hydroxynaphthalen-1-yl)methylideneamino]-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxamide
• CAS: 329789-76-6；672271-82-8
• 化学式: C₁₈H₁₆N₄O₂
• mdl: MFCD00611178
• 分子量: 320.351
• InChiKey: DXALFAYOYMDQMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  90.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氧代-2-(2-氧代环戊基)乙酸乙酯 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 42.0h， 生成 N'-[(2-hydroxynaphthalen-1-yl)methylene]-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbohydrazone
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors

  摘要：

  Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP‐4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP‐4 inhibitors, featuring the pyrazole‐3‐carbohydrazone scaffold, have been discovered using an integrated approach of structure‐based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low‐to‐mid‐micromolar inhibitory level compounds (1–5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k–l, and 7a–e) were found to show inhibitory effects against DPP‐4. Molecular docking models give rational explanation about structure–activity relationships. Based on eight DPP‐4 inhibitors (1–5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP‐4 inhibitors design.

  DOI：

  10.1111/j.1747-0285.2012.01365.x

文献信息

• Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors
  作者：Deyan Wu、Fangfang Jin、Weiqiang Lu、Jin Zhu、Cui Li、Wei Wang、Yun Tang、Hualiang Jiang、Jin Huang、Guixia Liu、Jian Li

  DOI：10.1111/j.1747-0285.2012.01365.x

  日期：2012.6

  Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP‐4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP‐4 inhibitors, featuring the pyrazole‐3‐carbohydrazone scaffold, have been discovered using an integrated approach of structure‐based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low‐to‐mid‐micromolar inhibitory level compounds (1–5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k–l, and 7a–e) were found to show inhibitory effects against DPP‐4. Molecular docking models give rational explanation about structure–activity relationships. Based on eight DPP‐4 inhibitors (1–5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP‐4 inhibitors design.