tert-butyl 4-[(piperidin-3-yl)carbonyl]piperazine-1-carboxylate | 1193387-72-2

• 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: tert-butyl 4-[(piperidin-3-yl)carbonyl]piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-(piperidine-3-carbonyl)piperazine-1-carboxylate
• CAS: 1193387-72-2
• 化学式: C₁₅H₂₇N₃O₃
• mdl: MFCD12913028
• 分子量: 297.398
• InChiKey: CGBRVCPIVDANCZ-UHFFFAOYSA-N

物化性质

• 沸点：
  447.2±45.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.866
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(piperidin-3-yl)carbonyl]piperazine-1-carboxylate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-{3-oxo-3-[4-(piperidine-3-carbonyl)piperazin-1-yl]propyl}-3H-quinazolin-4-one
  参考文献：
  名称：

  Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold

  摘要：

  Poly(ADP-ribose) polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl-piperazinylamides of 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.048
• 作为产物：
  描述：

  3-哌啶甲酸 、 N-Boc-哌嗪 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 4-[(piperidin-3-yl)carbonyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold

  摘要：

  Poly(ADP-ribose) polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl-piperazinylamides of 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.048

文献信息

• Discovery of Potent Isoindolinone Inhibitors that Target an Active Conformation of PARP1 Using DNA‐Encoded Libraries
  作者：Kelly A. McCarthy、Douglas J. Marcotte、Sangram Parelkar、Crystal L. McKinnon、Lindsay E. Trammell、Eric L. Stangeland、Rachael R. Jetson

  DOI：10.1002/cmdc.202400093

  日期：——

  Inhibition of poly (ADP‐ribose) polymerase‐1 (PARP1), a DNA repair enzyme, has proven to be a successful strategy for the treatment of various cancers. With the appropriate selection conditions and protein design, DNA‐encoded library (DEL) technology provides a powerful avenue to identify small molecules with the desired mechanism of action towards a target of interest. However, DNA‐binding proteins, such as PARP1, can be challenging targets for DEL screening due to non‐specific protein−DNA interactions. To overcome this, we designed and screened a PARP1 catalytic domain construct without the autoinhibitory helical domain. This allowed us to interrogate an active, functionally‐relevant form of the protein resulting in the discovery of novel isoindolinone PARP1 inhibitors with single‐digit nanomolar potency. These inhibitors also demonstrated little to no PARP1−DNA trapping, a property that could be advantageous in the clinic.
• Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold
  作者：Giuseppe Giannini、Gianfranco Battistuzzi、Loredana Vesci、Ferdinando M. Milazzo、Francesca De Paolis、Marcella Barbarino、Mario Berardino Guglielmi、Valeria Carollo、Grazia Gallo、Roberto Artali、Sabrina Dallavalle

  DOI：10.1016/j.bmcl.2013.12.048

  日期：2014.1

  Poly(ADP-ribose) polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a group of new potent PARP-1 inhibitors, acyl-piperazinylamides of 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-propionic acid. Molecular modeling studies highlighted the preponderant role of the propanoyl side chain. (C) 2013 Elsevier Ltd. All rights reserved.