3,6-diamino-2-(2-chlorobenzoyl)-4-(2-methoxyphenyl)thieno[2,3-b]pyridine-5-carbonitrile | 1286770-84-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,6-diamino-2-(2-chlorobenzoyl)-4-(2-methoxyphenyl)thieno[2,3-b]pyridine-5-carbonitrile
• CAS: 1286770-84-0
• 化学式: C₂₂H₁₅ClN₄O₂S
• 分子量: 434.906
• InChiKey: FHTNIHPBAJWDDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻甲氧基苯甲醛 在 哌啶 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3,6-diamino-2-(2-chlorobenzoyl)-4-(2-methoxyphenyl)thieno[2,3-b]pyridine-5-carbonitrile
  参考文献：
  名称：

  3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles Are Selective Inhibitors of Plasmodium falciparum Glycogen Synthase Kinase-3

  摘要：

  Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors. Being less active on GSK-3 homologues of other species, the title compounds showed selectivity in favor of PfGSK-3. Taking into account the X-ray structure of a related molecule in complex with human GSK-3 (HsGSK-3), a model was computed for the comparison of inhibitor complexes with the plasmodial and human enzymes. It was found that subtle differences in the ATP-binding pockets are responsible for the observed PfGSK-3 vs HsGSK-3 selectivity. Representatives of the title compound class exhibited micromolar IC₅₀ values against P. falciparum erythrocyte stage parasites. These results suggest that inhibitors of PfGSK-3 could be developed as potential antimalarial drugs.

  DOI：

  10.1021/jm301575n

文献信息

• New derivatives of thieno[2,3-b]pyridine and 5,6,7,8 tetrahydrothieno[2,3 b]quinoline in particular useful in the treatment of malaria
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：EP2308883A1

  公开（公告）日：2011-04-13

  The present invention is related to compounds of formula (I) in particular useful for the treatment of malaria, and to pharmaceutical compositions containing them.

  本发明涉及公式（I）的化合物，特别适用于治疗疟疾，并且涉及含有它们的制药组合物。
• 3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-<i>b</i>]pyridine-5-carbonitriles Are Selective Inhibitors of Plasmodium falciparum Glycogen Synthase Kinase-3
  作者：Wiebke Fugel、Anselm Erich Oberholzer、Bernhard Gschloessl、Ron Dzikowski、Narkiss Pressburger、Lutz Preu、Laurence H. Pearl、Blandine Baratte、Morgane Ratin、Ilya Okun、Christian Doerig、Sebastian Kruggel、Thomas Lemcke、Laurent Meijer、Conrad Kunick

  DOI：10.1021/jm301575n

  日期：2013.1.10

  Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors. Being less active on GSK-3 homologues of other species, the title compounds showed selectivity in favor of PfGSK-3. Taking into account the X-ray structure of a related molecule in complex with human GSK-3 (HsGSK-3), a model was computed for the comparison of inhibitor complexes with the plasmodial and human enzymes. It was found that subtle differences in the ATP-binding pockets are responsible for the observed PfGSK-3 vs HsGSK-3 selectivity. Representatives of the title compound class exhibited micromolar IC₅₀ values against P. falciparum erythrocyte stage parasites. These results suggest that inhibitors of PfGSK-3 could be developed as potential antimalarial drugs.