2-piperidin-1-yl-malonamide | 4711-17-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-piperidin-1-yl-malonamide
• 英文别名: piperidino-malonic acid diamide；Piperidino-malonsaeure-diamid；2-Piperidin-1-ylpropanediamide
• CAS: 4711-17-5
• 化学式: C₈H₁₅N₃O₂
• 分子量: 185.226
• InChiKey: NCGRFIZTDUCURQ-UHFFFAOYSA-N

物化性质

• 熔点：
  257 °C
• 沸点：
  388.0±37.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  89.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-piperidin-1-yl-malonamide 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2-(6-(2-fluorobenzyloxy)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-5-piperidinylpyrimidin-4,6-diamine
  参考文献：
  名称：

  Discovery of Novel Pyrazolo[3,4-b] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension

  摘要：

  Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-b] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds. In vitro, 2 exhibited moderate vasodilation activity and higher proliferation and migration suppressive effects compared to riociguat. In vivo, 2 significantly decreased right ventricular systolic pressure (RVSP), attenuated pulmonary artery medial thickness (PAMT), and right ventricular hypertrophy (RVH) in hypoxia-induced PAH rat models (i.g.). Given the unique advantages of significant vascular remodeling inhibition and moderate vascular relaxation based on the dual pathway regulation, we proposed 2 as a promising lead for anti-PAH drug discovery.

  DOI：

  10.1021/acs.jmedchem.0c01132
• 作为产物：
  描述：

  哌啶 在 氨 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 51.0h， 生成 2-piperidin-1-yl-malonamide
  参考文献：
  名称：

  Discovery of Novel Pyrazolo[3,4-b] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension

  摘要：

  Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-b] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds. In vitro, 2 exhibited moderate vasodilation activity and higher proliferation and migration suppressive effects compared to riociguat. In vivo, 2 significantly decreased right ventricular systolic pressure (RVSP), attenuated pulmonary artery medial thickness (PAMT), and right ventricular hypertrophy (RVH) in hypoxia-induced PAH rat models (i.g.). Given the unique advantages of significant vascular remodeling inhibition and moderate vascular relaxation based on the dual pathway regulation, we proposed 2 as a promising lead for anti-PAH drug discovery.

  DOI：

  10.1021/acs.jmedchem.0c01132

文献信息

• 448. Pyrimidine reactions. Part I. Pyrimidines from malondiamide
  作者：D. J. Brown

  DOI：10.1039/jr9560002312

  日期：——
• Complexes of technetium-99m with alkylene amine oximes
  申请人：AMERSHAM INTERNATIONAL plc

  公开号：EP0123504B1

  公开（公告）日：1989-09-20
• Discovery of Novel Pyrazolo[3,4-<i>b</i>] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension
  作者：Liqing Hu、Lijun Li、Qi Chang、Songsen Fu、Jia Qin、Zhuo Chen、Xiaohui Li、Qinglian Liu、Gaoyun Hu、Qianbin Li

  DOI：10.1021/acs.jmedchem.0c01132

  日期：2020.10.8

  Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-b] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds. In vitro, 2 exhibited moderate vasodilation activity and higher proliferation and migration suppressive effects compared to riociguat. In vivo, 2 significantly decreased right ventricular systolic pressure (RVSP), attenuated pulmonary artery medial thickness (PAMT), and right ventricular hypertrophy (RVH) in hypoxia-induced PAH rat models (i.g.). Given the unique advantages of significant vascular remodeling inhibition and moderate vascular relaxation based on the dual pathway regulation, we proposed 2 as a promising lead for anti-PAH drug discovery.