[3-(4-benzylpiperidin-1-yl)propyl]furan-2-ylmethylamine | 1606995-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [3-(4-benzylpiperidin-1-yl)propyl]furan-2-ylmethylamine
• 英文别名: 3-(4-benzylpiperidin-1-yl)-N-(furan-2-ylmethyl)propan-1-amine
• CAS: 1606995-55-4
• 化学式: C₂₀H₂₈N₂O
• 分子量: 312.455
• InChiKey: UUNRBEUBXCOJRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  28.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [3-(4-benzylpiperidin-1-yl)propyl]furan-2-ylmethylamine 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 2-[3-(4-Benzyl-piperidin-1-yl)-propyl]-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

  摘要：

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00680
• 作为产物：
  描述：

  糠醛 、 3-(4-benzylpiperidin-1-yl)propan-1-amine 在 sodium tetrahydroborate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 8.0h， 生成 [3-(4-benzylpiperidin-1-yl)propyl]furan-2-ylmethylamine
  参考文献：
  名称：

  Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

  摘要：

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00680