2-Oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine | 289654-94-0

• 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-Oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine
• 英文别名: 2-amino-1-(4-pyrimidin-2-ylpiperazin-1-yl)ethanone
• CAS: 289654-94-0
• 化学式: C₁₀H₁₅N₅O
• mdl: MFCD01475939
• 分子量: 221.262
• InChiKey: GXCLAVHQLLWTRT-UHFFFAOYSA-N

物化性质

• 沸点：
  464.3±55.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  异喹啉-5-磺酰氯 、 2-Oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 Isoquinolinesulfon-5-yl-[2-oxo-2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]amide
  参考文献：
  名称：

  From Tyrosine to Glycine:  Synthesis and Biological Activity of Potent Antagonists of the Purinergic P2X₇ Receptor

  摘要：

  The characterization of the native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective antagonists with a "druglike" profile. However, a tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. As a molecular simplification of KN-62, the present study was designed to evaluate the functional antagonistic properties of a novel series of glycine derivatives characterized by the presence of different phenyl-substituted piperazine moieties. Antagonistic activity of these glycine derivatives was tested on HEK293 cells transfected with the human P2X(7) receptor. The most potent P2X(7) receptor antagonist identified in this study (compound 4g) contains an o-fluorine substituent on the phenylpiperazine moiety and had an IC50 of 12.1 nM. The biological responses investigated were ATP-dependent Ca2+ influx across the plasma membrane and ethidium bromide uptake.

  DOI：

  10.1021/jm070443e
• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 21.5h， 生成 2-Oxo-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine
  参考文献：
  名称：

  取代的尿嘧啶衍生物可有效抑制聚（ADP-核糖）聚合酶-1（PARP-1）。

  摘要：

  合成了一类新的PARP-1抑制剂，即取代的稠合尿嘧啶衍生物。从IC（50）= 2microM的衍生物开始，化学优化程序导致化合物的效力增加了100倍以上（IC（50）<20nM）。另外，评估了理化和药代动力学性质。可以证明带有哌嗪或苯基取代的βAla-Gly侧链的化合物表现出最佳的整体性能。

  DOI：

  10.1016/s0960-894x(02)00602-9

文献信息

• Substituted amidoalkyl uracils and their use as inhibitors of the poly(adp-ribose) synthetase (pars)
  申请人：Albrecht Barbara

  公开号：US20050075347A1

  公开（公告）日：2005-04-07

  The invention relates to novel amidoalkyl uracil derivatives of formula (I), to a method for the production thereof, and to their use as medicament active substances for the prophylaxis and/or treatment of medical disorders.

  该发明涉及到化合物的新型酰胺烷基尿嘧啶衍生物（I）的公式，以及它们的生产方法，以及它们作为药物活性物质用于预防和/或治疗医学疾病。
• Design, Synthesis, and Biological Evaluation of a Series of Benzo[<i>de</i>][1,7]naphthyridin-7(8<i>H</i>)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors
  作者：Na Ye、Chuan-Huizi Chen、TianTian Chen、Zilan Song、Jin-Xue He、Xia-Juan Huan、Shan-Shan Song、Qiufeng Liu、Yi Chen、Jian Ding、Yechun Xu、Ze-Hong Miao、Ao Zhang

  DOI：10.1021/jm301825t

  日期：2013.4.11

  A series of benzo[de][1,7]naphthyridin-7(8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors. The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1(2H)-one framework and showing remarkably high PARP1 inhibitory activity (0.31 nM) but only moderate potency in the cell. Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0.26 nM). Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells. Significant potentiation on the cytotoxicity of Temozolomide was also observed. The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.
• SUBSTITUIERTE AMIDOALKYLURACILE UND IHRE VERWENDUNG ALS INHIBITOREN DER POLY (ADP-RIBOSE)-SYNTHETASE (PARS)
  申请人：Bayer Aktiengesellschaft

  公开号：EP1339699A1

  公开（公告）日：2003-09-03
• US7125995B2
  申请人：——

  公开号：US7125995B2

  公开（公告）日：2006-10-24
• [DE] SUBSTITUIERTE AMIDOALKYLURACILE UND IHRE VERWENDUNG ALS INHIBITOREN DER POLY (ADP-RIBOSE)-SYNTHETASE (PARS)<br/>[EN] SUBSTITUTED AMIDOALKYL URACILS AND THE USE THEREOF<br/>[FR] AMIDOALKYL-URACILES SUBSTITUES ET LEUR UTILISATION
  申请人：BAYER AG

  公开号：WO2002040455A1

  公开（公告）日：2002-05-23

  Es werden neue Amidoalkyluracil-Derivate der Formel (I), ein Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittelwirkstoffe zur Prophylaxe und/oder Behandlung von Erkrankungen beschrieben.