1-Pyrrolidin-1-ium-1-ylcyclopentane-1-carboxylate

• 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: 1-Pyrrolidin-1-ium-1-ylcyclopentane-1-carboxylate
• 化学式: C10H17NO2
• 分子量: 183.25
• InChiKey: RKEFYANFQKIQCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-[4-fluoro-3-(piperazin-1-ylcarbonyl)benzyl]-4,5-dimethylpyridazin-3(2H)-one 、 1-Pyrrolidin-1-ium-1-ylcyclopentane-1-carboxylate 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-(4-fluoro-3-(4-(1-(pyrrolidin-1-yl)cyclopentanecarbonyl)piperazine-1-carbonyl)benzyl)-4,5-dimethylpyridazin-3(2H)-one
  参考文献：
  名称：

  Development of substituted 6-[4-fluoro-3-(piperazin-1-ylcarbonyl)benzyl]-4,5-dimethylpyridazin-3(2H)-ones as potent poly(ADP–ribose) polymerase-1 (PARP-1) inhibitors active in BRCA deficient cells

  摘要：

  We describe an extensive SAR study in the 6-[4-fluoro-3-(substituted)benzyl]-4,5-dimethylpyridazin-3(2H)-one series which led to the identification of potent PARP-1 inhibitors, capable of inhibiting the proliferation of BRCA-1 deficient cancer cells in the low nanomolar range, and displaying >100-fold selectivity over the BRCA wild type counterparts. The series of compounds was devoid of hERG channel activity, and CYP inhibition and induction liabilities. Several analogs were stable in rat and human liver microsomes and displayed moderate rat clearance, with urinary excretion of parent as the major route of elimination. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.087

文献信息

• [EN] PREPARATION OF COMPLEXING AGENTS AND METAL ION COMPLEXES IN AQUEOUS MEDIA<br/>[FR] PRÉPARATION D'AGENTS COMPLEXANTS ET COMPLEXES D'IONS MÉTALLIQUES DANS DES MILIEUX AQUEUX
  申请人：MALLINCKRODT INC

  公开号：WO2007142804A2

  公开（公告）日：2007-12-13

  [EN] The invention relates to methods of preparation for bis-amide complexing agents, as well as paramagnetic metal ion complexes that include such agents. To prepare these complexing agents, a reaction mixture is formed that includes a bis-anhydride, a nitrogen-containing compound, and an aqueous solvent system. The nitrogen-containing compound reacts with the bis-anhydride in the reaction mixture to form the bis-amide complexing agent. The molar ratio of water to the nitrogen containing compound in the reaction mixture is greater than 3:1, respectively. In addition, the molar ratio of the nitrogen-containing compound to the bis-anhydride in the reaction mixture is no greater than 2.5:1, respectively. In some embodiments, a base other than the nitrogen-containing compound may be included in the reaction mixture (e.g., to buffer the reaction mixture). In some embodiments, the bis-amide complexing agent may be contacted with a paramagnetic metal ion salt to form a paramagnetic metal ion complex of the invention.
  [FR] L'invention concerne des procédés de préparation d'agents complexants de type bis-amide, ainsi que des complexes d'ions de métaux paramagnétiques qui comprennent de tels agents. Pour préparer ces agents complexants, on forme un mélange de réaction qui comprend un bis-anhydride, un composé contenant de l'azote et un système solvant aqueux. Le composé contenant de l'azote réagit avec le bis-anhydride dans le mélange de réaction pour former l'agent complexant de type bis-amide. La proportion molaire de l'eau par rapport au composé contenant de l'azote dans le mélange de réaction est supérieure à 3:1, respectivement. En plus, la proportion molaire du composé contenant de l'azote par rapport au bis-anhydride dans le mélange de réaction est inférieure ou égale à 2,5:1, respectivement. Dans certains modes de réalisation, une base autre que le composé contenant de l'azote peut être incluse dans le mélange de réaction (par exemple pour tamponner le mélange de réaction). Dans certains modes de réalisation, on peut mettre en contact l'agent complexant de type bis-amide avec un sel d'un ion d'un métal paramagnétique pour former un complexe d'un ion d'un métal paramagnétique de l'invention.
• Development of substituted 6-[4-fluoro-3-(piperazin-1-ylcarbonyl)benzyl]-4,5-dimethylpyridazin-3(2H)-ones as potent poly(ADP–ribose) polymerase-1 (PARP-1) inhibitors active in BRCA deficient cells
  作者：Federica Ferrigno、Danila Branca、Olaf Kinzel、Samuele Lillini、Laura Llauger Bufi、Edith Monteagudo、Ester Muraglia、Michael Rowley、Carsten Schultz-Fademrecht、Carlo Toniatti、Caterina Torrisi、Philip Jones

  DOI：10.1016/j.bmcl.2009.11.087

  日期：2010.2

  We describe an extensive SAR study in the 6-[4-fluoro-3-(substituted)benzyl]-4,5-dimethylpyridazin-3(2H)-one series which led to the identification of potent PARP-1 inhibitors, capable of inhibiting the proliferation of BRCA-1 deficient cancer cells in the low nanomolar range, and displaying >100-fold selectivity over the BRCA wild type counterparts. The series of compounds was devoid of hERG channel activity, and CYP inhibition and induction liabilities. Several analogs were stable in rat and human liver microsomes and displayed moderate rat clearance, with urinary excretion of parent as the major route of elimination. (C) 2009 Elsevier Ltd. All rights reserved.