Nα-(tert-butoxycarbonyl)-(4S)-{4-amino-5-[(2-pyridin-4-yl)ethyl]aminopentyl}-N'-nitroguanidine | 479644-61-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Nα-(tert-butoxycarbonyl)-(4S)-{4-amino-5-[(2-pyridin-4-yl)ethyl]aminopentyl}-N'-nitroguanidine
• 英文别名: N^α-(tert-butoxycarbonyl)-(4S)-{4-amino-5-[(2-pyridin-4-yl)ethyl]aminopentyl}-N'-nitroguanidine
• CAS: 479644-61-6
• 化学式: C₁₈H₃₁N₇O₄
• 分子量: 409.489
• InChiKey: DGTIQVFPBVWDSJ-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.19
• 重原子数：
  29.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  154.3
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Nα-(tert-butoxycarbonyl)-(4S)-{4-amino-5-[(2-pyridin-4-yl)ethyl]aminopentyl}-N'-nitroguanidine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以95%的产率得到N-{(4S)-4-amino-5-[(2-pyridin-4-ylethyl)amino]pentyl}-N''-nitroguanidine
  参考文献：
  名称：

  Aromatic Reduced Amide Bond Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase

  摘要：

  Nitric oxide synthase inhibitors could act as important therapies for disorders arising from overstimulation or overexpression of individual nitric oxide synthase (NOS) isoforms. But preservation of physiologically important nitric oxide functions require the use of isoform-selective inhibitors. Recently we reported reduced amide bond pseudodipeptide analogues as potent and selective neuronal nitric oxide synthase (nNOS) inhibitors (Hah, J.-M.; Roman, L. J.; Martasek, P.; Silverman, R. B. J. Med. Chem. 2001, 44, 2667-2670). To increase the lipophilicity a series of aromatic, reduced amide bond analogues (6-25) were designed and synthesized as potential selective nNOS inhibitors. The hypothesized large increase in isoform selectivity of nNOS over inducible NOS was not obtained in this series. However, the high potency with nNOS as well as high selectivity of nNOS over endothelial NOS was retained in some of these compounds (15, 17, 21), as well as good selectivity over inducible NOS. The most potent nNOS inhibitor among these compounds is N-(4S)-{4-amino-5-[2-(2-aminoethyl)phenylamino]-pentyl}-N'-nitroguanidine (17) (K-i = 50 nM), which also shows the highest selectivity over eNOS (greater than 2100-fold) and 70-fold selectivity over iNOS. Further modification of compound 17 should lead to even more potent and selective nNOS inhibitors.

  DOI：

  10.1021/jm0202932
• 作为产物：
  描述：

  在 三乙酰氧基硼氢化钠 作用下， 以 甲醇 为溶剂， 以400 mg的产率得到Nα-(tert-butoxycarbonyl)-(4S)-{4-amino-5-[(2-pyridin-4-yl)ethyl]aminopentyl}-N'-nitroguanidine
  参考文献：
  名称：

  Aromatic Reduced Amide Bond Peptidomimetics as Selective Inhibitors of Neuronal Nitric Oxide Synthase

  摘要：

  Nitric oxide synthase inhibitors could act as important therapies for disorders arising from overstimulation or overexpression of individual nitric oxide synthase (NOS) isoforms. But preservation of physiologically important nitric oxide functions require the use of isoform-selective inhibitors. Recently we reported reduced amide bond pseudodipeptide analogues as potent and selective neuronal nitric oxide synthase (nNOS) inhibitors (Hah, J.-M.; Roman, L. J.; Martasek, P.; Silverman, R. B. J. Med. Chem. 2001, 44, 2667-2670). To increase the lipophilicity a series of aromatic, reduced amide bond analogues (6-25) were designed and synthesized as potential selective nNOS inhibitors. The hypothesized large increase in isoform selectivity of nNOS over inducible NOS was not obtained in this series. However, the high potency with nNOS as well as high selectivity of nNOS over endothelial NOS was retained in some of these compounds (15, 17, 21), as well as good selectivity over inducible NOS. The most potent nNOS inhibitor among these compounds is N-(4S)-{4-amino-5-[2-(2-aminoethyl)phenylamino]-pentyl}-N'-nitroguanidine (17) (K-i = 50 nM), which also shows the highest selectivity over eNOS (greater than 2100-fold) and 70-fold selectivity over iNOS. Further modification of compound 17 should lead to even more potent and selective nNOS inhibitors.

  DOI：

  10.1021/jm0202932