tert-butyl (S)-4-methyl-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-ylcarbamate | 1616684-40-2

• 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: tert-butyl (S)-4-methyl-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-ylcarbamate
• 英文别名: (S)-tert-butyl (4-methyl-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-yl)carbamate
• CAS: 1616684-40-2
• 化学式: C₁₆H₃₁N₃O₃
• 分子量: 313.44
• InChiKey: PZBGWOVWYGIQBT-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  61.88
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-4-methyl-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-ylcarbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 苯酚 为溶剂， 生成 (S)-2-(7-chloroquinolin-4-ylamino)-4-methyl-1-(4-methylpiperazin-1-yl)pentan-1-one
  参考文献：
  名称：

  Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain

  摘要：

  Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β(3)- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.

  DOI：

  10.1016/j.bmc.2014.05.024
• 作为产物：
  描述：

  L-亮氨酸 、 二碳酸二叔丁酯 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 生成 tert-butyl (S)-4-methyl-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-ylcarbamate
  参考文献：
  名称：

  Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain

  摘要：

  Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β(3)- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI=5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.

  DOI：

  10.1016/j.bmc.2014.05.024

文献信息

• Discovery and Pharmacophore Mapping of a Low‐Nanomolar Inhibitor of <i>P. falciparum</i> Growth
  作者：Ivan Bassanini、Silvia Parapini、Corinna Galli、Nadia Vaiana、Andrea Pancotti、Nicoletta Basilico、Donatella Taramelli、Sergio Romeo

  DOI：10.1002/cmdc.201900526

  日期：2019.12.4

  of Plasmodium, especially P. falciparum (Pf). In this view, the development of new antiplasmodial agents that are able to act via innovative mechanisms of action, is crucial to ensure efficacious antimalarial treatments. In one of our previous communications, we described a novel class of compounds endowed with high antiplasmodial activity, characterized by a pharmacophore never described before as

  疟疾是全世界最常见的寄生虫病，是继艾滋病毒和结核病之后第三致命的感染。目前，由于疟原虫在各种疟原虫中，尤其是恶性疟原虫（Pf）的耐药性急剧增加和扩散，疟疾的治疗方法受到损害。按照这种观点，能够通过创新的作用机制起作用的新抗疟原虫药物的开发对于确保有效的抗疟疾治疗至关重要。在我们以前的通讯中，我们描述了具有高抗血浆活性的一类新型化合物，其特征是以前从未描述为抗血浆的药效团，并通过它们的4,4'-氧双苯甲酰胺基核心进行了鉴定。在这里，通过详细的结构-活动关系（SAR）研究，我们彻底研究了所报道的支架的化学特征，并成功地构建了一种新型的抗血浆药物，该药物对氯喹（CQ）敏感和耐CQ的Pf菌株在低纳摩尔范围内均具有活性，而没有表现出交叉耐药性。此外，我们进行了计算机模拟药效团映射。