1-glycyl-3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2-dimethylimidazolidin-4-one | 1056898-60-2

• 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-glycyl-3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2-dimethylimidazolidin-4-one
• 英文别名: 1-(2-amino-1-oxoethyl)-3-{4-[(6-methoxyquinolin-8-yl)amino]-pentyl}-2,2-dimethylimidazolidin-4-one；1-(2-Aminoacetyl)-3-[4-[(6-methoxy-8-quinolyl)amino]pentyl]-2,2-dimethyl-imidazolidin-4-one；1-(2-aminoacetyl)-3-[4-[(6-methoxyquinolin-8-yl)amino]pentyl]-2,2-dimethylimidazolidin-4-one
• CAS: 1056898-60-2
• 化学式: C₂₂H₃₁N₅O₃
• 分子量: 413.52
• InChiKey: AOONPRNLKHTSCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-[(N-tert-butyloxycarbonyl)glycyl]-3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2-dimethylimidazolidin-4-one 在 三氟乙酸 、 sodium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 1-glycyl-3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2-dimethylimidazolidin-4-one
  参考文献：
  名称：

  氨基酸作为选择性酰化剂：抗疟药伯氨喹的咪唑啉丁-4-酮衍生物的区域选择性N 1-酰化

  摘要：

  使用的生物活性基于伯-咪唑烷-4-酮的酰化进行了研究Ñ α -Boc保护的甘氨酸作为酰化剂。比较了两种合成路线，八种不同的偶联方法和七种不同的溶剂。在高介电常数溶剂（例如DMF或MeCN）上基于碳二亚胺的轻度偶联提高了酰化收率，而醇类则抑制了碳二亚胺介导的酰化反应。合成目标的实现受限于咪唑烷基-4-酮环取代基R 1，R 2和R 3的大小，但诉诸于MW辅助合成可以克服此类障碍，尽管反应收率非常适中。涉及所用Boc保护的氨基酸的所有反应均具有区域选择性，而与所采用的反应条件无关。相比之下，咪唑烷丁-4-酮的区域选择性乙酰化只能通过非常温和的偶联程序来实现。

  DOI：

  10.1016/j.tet.2008.09.058

文献信息

• Imidazolidin-4-one peptidomimetic derivatives of primaquine: Synthesis and antimalarial activity
  作者：Nuno Vale、Joana Matos、Jiri Gut、Fátima Nogueira、Virgílio do Rosário、Philip J. Rosenthal、Rui Moreira、Paula Gomes

  DOI：10.1016/j.bmcl.2008.05.076

  日期：2008.7

  The synthesis of imidazolidin-4-one derivatives of primaquine containing the five-membered ring at the C-terminus of a dipeptide backbone coupled to the parent drug is described. These peptidomimetic derivatives were active against a chloroquine-resistant Plasmodium falciparum strain and inhibited the development of the sporogonic cycle of Plasmodium berghei, affecting the appearance of oocysts in

  描述了在与母体药物偶联的二肽主链的C末端含有五元环的伯氨喹的咪唑烷二-4-酮衍生物的合成。这些拟肽衍生物对抗氯喹的恶性疟原虫菌株具有活性，并抑制了伯氏疟原虫的孢子周期的发展，影响了蚊子中肠内卵囊的出现。由于N（1）的酰化作用，新型的咪唑烷基-4-酮在人血浆和pH 7.4缓冲液中都极为稳定。因此，衍生自二肽基8-氨基喹啉的“内部”咪唑啉丁-4-酮代表了抗疟疾结构-活性关系中的一个新条目。
• Amino acids as selective acylating agents: regioselective N1-acylation of imidazolidin-4-one derivatives of the antimalarial drug primaquine
  作者：Nuno Vale、Joana Matos、Rui Moreira、Paula Gomes

  DOI：10.1016/j.tet.2008.09.058

  日期：2008.12

  The acylation of bioactive primaquine-based imidazolidin-4-ones was studied using Nα-Boc-protected glycine as acylating agent. Two synthesis routes, eight different coupling methods and seven distinct solvents were compared. Mild carbodiimide-based couplings on high dielectric constant solvents such as DMF or MeCN increased acylation yields, whereas alcohols inhibited carbodiimide-mediated acylations

  使用的生物活性基于伯-咪唑烷-4-酮的酰化进行了研究Ñ α -Boc保护的甘氨酸作为酰化剂。比较了两种合成路线，八种不同的偶联方法和七种不同的溶剂。在高介电常数溶剂（例如DMF或MeCN）上基于碳二亚胺的轻度偶联提高了酰化收率，而醇类则抑制了碳二亚胺介导的酰化反应。合成目标的实现受限于咪唑烷基-4-酮环取代基R 1，R 2和R 3的大小，但诉诸于MW辅助合成可以克服此类障碍，尽管反应收率非常适中。涉及所用Boc保护的氨基酸的所有反应均具有区域选择性，而与所采用的反应条件无关。相比之下，咪唑烷丁-4-酮的区域选择性乙酰化只能通过非常温和的偶联程序来实现。
• Imidazoquines as Antimalarial and Antipneumocystis Agents
  作者：Nuno Vale、Miguel Prudêncio、Catarina A. Marques、Margaret S. Collins、Jiri Gut、Fátima Nogueira、Joana Matos、Philip J. Rosenthal、Melanie T. Cushion、Virgílio E. do Rosário、Maria M. Mota、Rui Moreira、Paula Gomes

  DOI：10.1021/jm900738c

  日期：2009.12.10

  Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria front mouse to mosquito and be highly stable toward hydrolysis at physiological conditions. This prompted Lis to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines' stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes.