(2S)-1-[2-(3-oxo-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carbonitrile | 1428264-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (2S)-1-[2-(3-oxo-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carbonitrile
• CAS: 1428264-56-5
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: JNHNUZDMIYRMDE-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  异吲哚啉-1-酮 、 (2S)-N-氯乙酰基-2-氰基四氢吡咯 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 1.0h， 以36%的产率得到(2S)-1-[2-(3-oxo-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold

  摘要：

  Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.

  DOI：

  10.1021/ml300410d

文献信息

• Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold
  作者：Koen Jansen、Leen Heirbaut、Jonathan D. Cheng、Jurgen Joossens、Oxana Ryabtsova、Paul Cos、Louis Maes、Anne-Marie Lambeir、Ingrid De Meester、Koen Augustyns、Pieter Van der Veken

  DOI：10.1021/ml300410d

  日期：2013.5.9

  Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.