1-(3,4-methylenedioxybenzyl)-4-(pyrrolidinocarbonylmethyl)piperazine | 119963-77-8

• 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: 1-(3,4-methylenedioxybenzyl)-4-(pyrrolidinocarbonylmethyl)piperazine
• 英文别名: 2-[4-(1,3-Benzodioxol-5-ylmethyl)piperazin-1-yl]-1-pyrrolidin-1-ylethanone
• CAS: 119963-77-8
• 化学式: C₁₈H₂₅N₃O₃
• 分子量: 331.415
• InChiKey: OIHOSALNMPFTIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 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：

  1-(氯乙酰基)吡咯烷 、 1-胡椒基哌嗪 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 1-(3,4-methylenedioxybenzyl)-4-(pyrrolidinocarbonylmethyl)piperazine
  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

• Benzylpiperazine derivatives. IX. Structure-antiulcer activity studies of 1-(aminocarbonylalkyl)-4-benzylpiperazine derivatives by the adaptive least-squares method.
  作者：HIROSHI OHTAKA、KENJI YOSHIDA、KENJI SUZUKI

  DOI：10.1248/cpb.36.3955

  日期：——

  Quantitative structure-antiulcer activity relationships of 1-(aminocarbonylalkyl)-4-benzylpiperazine derivatives (I) were analyzed by using the adaptive least-squares (ALS) technique. Discriminant functions show that (1) a bulky amide moiety is disadvantageous, (2) a small number of methylene groups between carbonyl and piperazine is favorable, (3) a substituent which has a large B1 value (or B2 value when the substituent is forced to be in the in-plane conformation) with low lipophilicity at the 3 and/or 4 position of the benzyl moiety is favorable for antiulcer activity with low acute toxicity.

  1-(氨基羰基烷基)-4-苄基哌嗪衍生物（I）的定量结构-抗溃疡活性关系通过自适应最小二乘（ALS）技术进行了分析。判别函数表明：（1）笨重的酰胺部分是不利的；（2）羰基和哌嗪之间有少量亚甲基是有利的；（3）在苄基部分的3和/或4位具有大B1值（或B2值，当取代基被迫处于面内构象时）和低亲脂性的取代基有利于抗溃疡活性，急性毒性低。