2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]-1-piperidin-1-ylethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]-1-piperidin-1-ylethanone
• 化学式: C₁₉H₂₇N₃O₃
• 分子量: 345.442
• InChiKey: PXBCLZANKFSJIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  45.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯-1-哌啶-1-基乙酮 、 1-胡椒基哌嗪 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]-1-piperidin-1-ylethanone
  参考文献：
  名称：

  Design, Synthesis, Biological Screening, and Molecular Docking Studies of Piperazine-Derived Constrained Inhibitors of DPP-IV for the Treatment of Type 2 Diabetes

  摘要：

  Novel piperazine‐derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase‐IV (DPP‐IV) inhibitory activities. From a library of compounds synthesized, 1‐(2‐(4‐(7‐Chloro‐4‐quinolyl)piperazin‐1‐yl)acetyl)pyrrolidine (2g) was identified as a potential DPP‐IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two‐week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP‐IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.

  DOI：

  10.1111/cbdd.12426

文献信息

• Design, Synthesis, Biological Screening, and Molecular Docking Studies of Piperazine-Derived Constrained Inhibitors of DPP-IV for the Treatment of Type 2 Diabetes
  作者：Ram N. Kushwaha、Rohit Srivastava、Akansha Mishra、Arun K. Rawat、Arvind K. Srivastava、Wahajul Haq、Seturam B. Katti

  DOI：10.1111/cbdd.12426

  日期：2015.4

  Novel piperazine‐derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase‐IV (DPP‐IV) inhibitory activities. From a library of compounds synthesized, 1‐(2‐(4‐(7‐Chloro‐4‐quinolyl)piperazin‐1‐yl)acetyl)pyrrolidine (2g) was identified as a potential DPP‐IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two‐week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP‐IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.