3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2,5-trimethylimidazolidin-4-one | 737004-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2,5-trimethylimidazolidin-4-one
• 英文别名: PQ-Ala-Acetone；(5S)-3-[4-[(6-methoxy-8-quinolyl)amino]pentyl]-2,2,5-trimethyl-imidazolidin-4-one；(5S)-3-[4-[(6-methoxyquinolin-8-yl)amino]pentyl]-2,2,5-trimethylimidazolidin-4-one
• CAS: 737004-42-1
• 化学式: C₂₁H₃₀N₄O₂
• 分子量: 370.495
• InChiKey: KJTHKMJERXZIQY-LOACHALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  BOC-甘氨酸 、 3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2,5-trimethylimidazolidin-4-one 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到1-[(N-tert-butyloxycarbonyl)glycyl]-3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2,5-trimethylimidazolidin-4-one
  参考文献：
  名称：

  伯氨喹的咪唑啉丁-4-酮拟肽衍生物：合成和抗疟活性。

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2008.05.076
• 作为产物：
  描述：

  磷酸伯氨喹 在 4 A molecular sieve 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 192.0h， 生成 3-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}-2,2,5-trimethylimidazolidin-4-one
  参考文献：
  名称：

  伯氨喹的咪唑啉丁-4-酮和1 H-咪唑并[2,1 - a ]异吲哚-2,5（3 H，9b H）-二酮衍生物的合成：范围和局限性

  摘要：

  描述了伯氨喹的咪唑啉丁-4-酮衍生物作为潜在的抗疟药的合成。在三个步骤中合成的目标化合物：（ⅰ）的缩合（±）-primaquine用N α -保护的氨基酸，（ⅱ）除去N-的α保护基团，和（iii）的N acylprimaquine与反应羰基化合物：丙酮，三个环酮和藜芦醛。在得到第三步骤，使用2-甲酰基苯甲酸1 H ^ -咪唑并[2,1-一个]异吲哚-2,5（3 ħ，9B ħ） -二酮。分离出的所有产物均具有良好的收率。咪唑啉丁-4-酮是所有可能的非对映异构体的等量混合物，而1 H-咪唑并[2,1-以立体选择性的方式产生]异吲哚-2,5（3 H，9b H）-二酮。化合物在pH 7.4缓冲液中水解非常缓慢（t 1/2 5–30 d），释放出伯氨喹。这些伯氨喹衍生物正在接受生物学检测，其抗疟活性的初步结果令人鼓舞。

  DOI：

  10.1016/j.tet.2004.04.077

文献信息

• 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.
• Anti-tumoral activity of imidazoquines, a new class of antimalarials derived from primaquine
  作者：Iva Fernandes、Nuno Vale、Victor de Freitas、Rui Moreira、Nuno Mateus、Paula Gomes

  DOI：10.1016/j.bmcl.2009.10.081

  日期：2009.12

  The growth inhibitory activity of imidazoquines, antimalarial imidazolidin-4-ones derived from primaquine, on human cancer cell lines HT-29, Caco-2, and MCF-7 has been evaluated. Primaquine, N-dipeptidyl-primaquine derivatives, and other quinolines have been included in the study for comparison purposes. Primaquine and some of its derivatives were significantly active against the MCF-7 human breast cancer cell line, so these compounds might represent useful leads targeted at the development of novel specific agents against breast cancer. Conversely, all compounds were generally inactive against HT-29, with only one of the imidazoquines having IC50 below 50 mu M. Activities against the Caco-2 cell line were modest and did not follow any defined trend. (C) 2009 Elsevier Ltd. All rights reserved.
• Anti-Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-ones
  作者：Nuno Vale、Margaret S. Collins、Jiri Gut、Ricardo Ferraz、Philip J. Rosenthal、Melanie T. Cushion、Rui Moreira、Paula Gomes

  DOI：10.1016/j.bmcl.2007.11.105

  日期：2008.1

  A series of primaquine-derived imidazolidin-4-ones were screened for their in vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain. Most compounds were active against P. carinii above 10 mu g/mL and displayed slight to marked activity. The imidazolidin-4-ones most active against P. carinii were also those most active antiplasmodial agents, in the mu M range. One of the tested imidazolidin-4-ones was slightly more active than the parent primaquine and may represent a lead compound for the development of novel anti-P. carinii 8-aminoquinolines with increased stability and resistance to metabolic inactivation. (c) 2007 Elsevier Ltd. All rights reserved.
• 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。
• Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of primaquine: scope and limitations
  作者：Paula Gomes、Maria João Araújo、Manuela Rodrigues、Nuno Vale、Zélia Azevedo、Jim Iley、Paula Chambel、José Morais、Rui Moreira

  DOI：10.1016/j.tet.2004.04.077

  日期：2004.6

  The synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (±)-primaquine with Nα-protected amino acids, (ii) removal of the Nα-protecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic

  描述了伯氨喹的咪唑啉丁-4-酮衍生物作为潜在的抗疟药的合成。在三个步骤中合成的目标化合物：（ⅰ）的缩合（±）-primaquine用N α -保护的氨基酸，（ⅱ）除去N-的α保护基团，和（iii）的N acylprimaquine与反应羰基化合物：丙酮，三个环酮和藜芦醛。在得到第三步骤，使用2-甲酰基苯甲酸1 H ^ -咪唑并[2,1-一个]异吲哚-2,5（3 ħ，9B ħ） -二酮。分离出的所有产物均具有良好的收率。咪唑啉丁-4-酮是所有可能的非对映异构体的等量混合物，而1 H-咪唑并[2,1-以立体选择性的方式产生]异吲哚-2,5（3 H，9b H）-二酮。化合物在pH 7.4缓冲液中水解非常缓慢（t 1/2 5–30 d），释放出伯氨喹。这些伯氨喹衍生物正在接受生物学检测，其抗疟活性的初步结果令人鼓舞。