2-amino-N-cyclopentylisonicotinamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-amino-N-cyclopentylisonicotinamide
• 英文别名: 2-amino-N-cyclopentylpyridine-4-carboxamide
• 化学式: C₁₁H₁₅N₃O
• 分子量: 205.26
• InChiKey: AHOKKZBAACXYHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-(isocyanomethyl)phenyl)-2,3-di-Boc-guanidine 、 2-amino-N-cyclopentylisonicotinamide 、 乙醛酸水合物 在 高氯酸 作用下， 以 甲醇 、 水 为溶剂， 反应 6.5h， 以43%的产率得到(Z)-N-cyclopentyl-3-((4-(2,3-di-Boc-guanidino)benzyl)amino)imidazo[1,2-a]pyridine-7-carboxamide
  参考文献：
  名称：

  Discovery and SAR of Novel and Selective Inhibitors of Urokinase Plasminogen Activator (uPA) with an Imidazo[1,2-a]pyridine Scaffold

  摘要：

  Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types. Its inhibition is regarded as a promising, noncytotoxic approach in cancer therapy by blocking growth and/or metastasis of solid tumors. Earlier, we reported the modified substrate activity screening (MSAS) approach and applied it for the identification of fragments with affinity for uPA's Si pocket. Here, these fragments are transformed into a novel class of uPA inhibitors with an imidazo[1,2-a]pyridine scaffold. The SAR for uPA inhibition around this scaffold is explored, and the best compounds in the series have nanomolar uPA affinity and selectivity with respect to the related trypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa). Finally, the approach followed for translating fragments into small molecules with a decorated scaffold architecture is conceptually straightforward and can be expected to be broadly applicable in fragment-based drug design.

  DOI：

  10.1021/acs.jmedchem.5b01171
• 作为产物：
  描述：

  2-氨基异烟酸甲酯 、 环戊胺 在 1,5,7-三氮杂双环[4.4.0]癸-5-烯 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以90%的产率得到2-amino-N-cyclopentylisonicotinamide
  参考文献：
  名称：

  Discovery and SAR of Novel and Selective Inhibitors of Urokinase Plasminogen Activator (uPA) with an Imidazo[1,2-a]pyridine Scaffold

  摘要：

  Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types. Its inhibition is regarded as a promising, noncytotoxic approach in cancer therapy by blocking growth and/or metastasis of solid tumors. Earlier, we reported the modified substrate activity screening (MSAS) approach and applied it for the identification of fragments with affinity for uPA's Si pocket. Here, these fragments are transformed into a novel class of uPA inhibitors with an imidazo[1,2-a]pyridine scaffold. The SAR for uPA inhibition around this scaffold is explored, and the best compounds in the series have nanomolar uPA affinity and selectivity with respect to the related trypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa). Finally, the approach followed for translating fragments into small molecules with a decorated scaffold architecture is conceptually straightforward and can be expected to be broadly applicable in fragment-based drug design.

  DOI：

  10.1021/acs.jmedchem.5b01171

文献信息

• Discovery and SAR of Novel and Selective Inhibitors of Urokinase Plasminogen Activator (uPA) with an Imidazo[1,2-<i>a</i>]pyridine Scaffold
  作者：Rafaela Gladysz、Yves Adriaenssens、Hans De Winter、Jurgen Joossens、Anne-Marie Lambeir、Koen Augustyns、Pieter Van der Veken

  DOI：10.1021/acs.jmedchem.5b01171

  日期：2015.12.10

  Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types. Its inhibition is regarded as a promising, noncytotoxic approach in cancer therapy by blocking growth and/or metastasis of solid tumors. Earlier, we reported the modified substrate activity screening (MSAS) approach and applied it for the identification of fragments with affinity for uPA's Si pocket. Here, these fragments are transformed into a novel class of uPA inhibitors with an imidazo[1,2-a]pyridine scaffold. The SAR for uPA inhibition around this scaffold is explored, and the best compounds in the series have nanomolar uPA affinity and selectivity with respect to the related trypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa). Finally, the approach followed for translating fragments into small molecules with a decorated scaffold architecture is conceptually straightforward and can be expected to be broadly applicable in fragment-based drug design.