N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]pyridine-4-sulfonamide | 854529-09-2

• 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: N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]pyridine-4-sulfonamide
• CAS: 854529-09-2
• 化学式: C₂₀H₂₀N₆O₂S
• 分子量: 408.484
• InChiKey: APEWSBHEFGTAOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]pyridine-4-sulfonamide 、 N-tert-butyl-2-bromoacetamide 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-tert-butyl-2-[[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]-pyridin-4-ylsulfonylamino]acetamide
  参考文献：
  名称：

  Protein Farnesyltransferase Inhibitors Exhibit Potent Antimalarial Activity

  摘要：

  New therapeutics to combat malaria are desperately needed. Here we show that the enzyme protein farnesyltransferase (PFT) from the malaria parasite Plasmodium falciparum (P. falciparum) is an ideal drug target. PFT inhibitors (PFTIs) are well tolerated in man, but are highly cytotoxic to P. falciparum. Because of their anticancer properties, PFTIs comprise a highly developed class of compounds. PFTIs are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously garnered information. Low nanomolar concentrations of tetrahydroquinoline (THQ)-based PFTIs inhibit P. falciparum PFT and are cytotoxic to cultured parasites. Biochemical studies suggest inhibition of parasite PFT as the mode of THQ cytotoxicity. Studies with malaria-infected mice show that THQ PFTIs dramatically reduce parasitemia and lead to parasite eradication in the majority of animals. These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity.

  DOI：

  10.1021/jm0491039
• 作为产物：
  描述：

  吡啶-4-磺酰氯 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 50.0h， 生成 N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]pyridine-4-sulfonamide
  参考文献：
  名称：

  Protein Farnesyltransferase Inhibitors Exhibit Potent Antimalarial Activity

  摘要：

  New therapeutics to combat malaria are desperately needed. Here we show that the enzyme protein farnesyltransferase (PFT) from the malaria parasite Plasmodium falciparum (P. falciparum) is an ideal drug target. PFT inhibitors (PFTIs) are well tolerated in man, but are highly cytotoxic to P. falciparum. Because of their anticancer properties, PFTIs comprise a highly developed class of compounds. PFTIs are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously garnered information. Low nanomolar concentrations of tetrahydroquinoline (THQ)-based PFTIs inhibit P. falciparum PFT and are cytotoxic to cultured parasites. Biochemical studies suggest inhibition of parasite PFT as the mode of THQ cytotoxicity. Studies with malaria-infected mice show that THQ PFTIs dramatically reduce parasitemia and lead to parasite eradication in the majority of animals. These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity.

  DOI：

  10.1021/jm0491039

文献信息

• Protein Farnesyltransferase Inhibitors Exhibit Potent Antimalarial Activity
  作者：Laxman Nallan、Kevin D. Bauer、Pravin Bendale、Kasey Rivas、Kohei Yokoyama、Carolyn P. Hornéy、Prakash Rao Pendyala、David Floyd、Louis J. Lombardo、David K. Williams、Andrew Hamilton、Said Sebti、William T. Windsor、Patricia C. Weber、Frederick S. Buckner、Debopam Chakrabarti、Michael H. Gelb、Wesley C. Van Voorhis

  DOI：10.1021/jm0491039

  日期：2005.6.1

  New therapeutics to combat malaria are desperately needed. Here we show that the enzyme protein farnesyltransferase (PFT) from the malaria parasite Plasmodium falciparum (P. falciparum) is an ideal drug target. PFT inhibitors (PFTIs) are well tolerated in man, but are highly cytotoxic to P. falciparum. Because of their anticancer properties, PFTIs comprise a highly developed class of compounds. PFTIs are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously garnered information. Low nanomolar concentrations of tetrahydroquinoline (THQ)-based PFTIs inhibit P. falciparum PFT and are cytotoxic to cultured parasites. Biochemical studies suggest inhibition of parasite PFT as the mode of THQ cytotoxicity. Studies with malaria-infected mice show that THQ PFTIs dramatically reduce parasitemia and lead to parasite eradication in the majority of animals. These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity.