Indazol-5-ylaminomethylen-malonsaeure-diethylester | 68535-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: Indazol-5-ylaminomethylen-malonsaeure-diethylester
• 英文别名: [(1(2)H-indazol-5-ylamino)-methylene]-malonic acid diethyl ester；Diethyl [(1h-indazol-5-ylamino)methylidene]propanedioate；diethyl 2-[(1H-indazol-5-ylamino)methylidene]propanedioate
• CAS: 68535-06-8
• 化学式: C₁₅H₁₇N₃O₄
• 分子量: 303.318
• InChiKey: GKXNONPLTPYLCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Indazol-5-ylaminomethylen-malonsaeure-diethylester 在 Gilotherm 作用下， 反应 0.17h， 以70%的产率得到9-Oxo-6,9-dihydro-3H-pyrazolo<4,3-f>chinolin-8-carbonsaeureethylester
  参考文献：
  名称：

  Le Hao Dong; Coquelet; Bastide, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 119 - 124

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氨基吲唑 、 乙氧基甲叉丙二酸二乙酯 反应 0.5h， 以90%的产率得到Indazol-5-ylaminomethylen-malonsaeure-diethylester
  参考文献：
  名称：

  Le Hao Dong; Coquelet; Bastide, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 119 - 124

  摘要：

  DOI：

文献信息

• Regioselective Synthesis of 5- and 3-Hydroxy-N-Aryl-1H-Pyrazole-4-Carboxylates and Their Evaluation as Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase
  作者：Luka Vah、Tadej Medved、Uroš Grošelj、Marina Klemenčič、Črtomir Podlipnik、Bogdan Štefane、Jernej Wagger、Marko Novinec、Jurij Svete

  DOI：10.3390/molecules27154764

  日期：——

  pyrazole derivatives for the inhibition of PfDHODH showed that 1-(naphthalene-2-yl)-5-hydroxy-1H-pyrazole-4-carboxylate and 1-(naphthalene-2-yl)-, 1-(2,4,6-trichlorophenyl)-, and 1-[4-(trifluoromethyl)phenyl]-3-hydroxy-1H-pyrazole-4-carboxylates (~30% inhibition) were slightly more potent than a known inhibitor, diethyl α-[(1H-indazol-5-yl)amino]methylidene}malonate (19% inhibition).

  对各种区域异构体 5- 和 3-羟基取代的烷基 1-芳基-1 H-吡唑-4-羧酸酯及其无环前体的计算机评估在它们与恶性疟原虫二氢乳清酸脱氢酶活性位点的结合方面产生了有希望的结果（Pf DHODH）。因此，通过烯胺酮型试剂或关键中间体通过两步合成制备了四种1-芳基-5-羟基-1H-吡唑-4-甲酸乙酯及其3-羟基区域异构体。使用文献方案进行5-羟基-1H-吡唑的合成，包括酸催化[(二甲基氨基)亚甲基]丙二酸二乙酯与芳基肼的氨基转移，随后碱催化中间体腙的环化。为了合成异构的1-芳基-3-羟基-1H-吡唑-4-羧酸甲酯，开发了一种新型的两步合成方法。其包括用甲基丙二酰氯酰化肼，然后用叔丁氧基-双(二甲氨基)甲烷环化肼。测试吡唑衍生物对Pf DHODH的抑制作用表明，1-(萘-2-基)-5-羟基-1 H-吡唑-4-羧酸酯和 1-(萘-2-基)-, 1-(2 ,4,6-三氯苯基)-和 1-[4-(三氟甲基)苯基]-3-羟基-1
• Design and Synthesis of Potent Inhibitors of the Malaria Parasite Dihydroorotate Dehydrogenase
  作者：Timo Heikkilä、Christopher Ramsey、Matthew Davies、Christophe Galtier、Andrew M. W. Stead、A. Peter Johnson、Colin W. G. Fishwick、Andrew N. Boa、Glenn A. McConkey

  DOI：10.1021/jm060687j

  日期：2007.1.1

  Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with low nanomolar binding affinities were identified that bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate. These compounds also prevented growth of cultured parasites at low micromolar concentrations. Models that suggest the mode of inhibitor binding is based on shape complementarity, matching hydrophobic regions of inhibitor and enzyme, and interaction of inhibitors with amino acid residues F188, H185, and R265 are supported by mutagenesis data. These results further highlight PfDHODH as a promising new target for chemotherapeutic intervention in prevention of malaria and provide better understanding of the factors that determine specificity over human dihydroorotate dehydrogenase.
• Synthesis and evaluation of a series of aryl[e]fused pyrazolo[4,3-c]pyridines with potential anxiolytic activity
  作者：Ian T. Forbes、Christopher N. Johnson、Graham E. Jones、Julia Loudon、Jane M. Nicholass、Mervyn Thompson、Neil Upton

  DOI：10.1021/jm00171a046

  日期：1990.9

  A series of pyrazolo[4,3-c]pyridines has been synthesized and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different from that of diazepam. A number of the compounds possess higher affinity for central benzodiazepine receptors than diazepam, yet show less anticonvulsant activity and are less sedative. The structure-activity relationships of these potential anxiolytic agents are discussed.
• LE HAO DONG P.; COQUELET C.; BASTIDE J.-M.; LEBECO J.-C., EUR. J. MED. CHEM.-CHIM. THER., 1980, 15, NO 2, 119-124
  作者：LE HAO DONG P.、 COQUELET C.、 BASTIDE J.-M.、 LEBECO J.-C.

  DOI：——

  日期：——
• KAMETANI TETSUJI; KIGASAWARA KAZUO; HIIRAGI MINEHARU; WAKISAKA KIKUO; HAG+, YAKUGAKU DZASSI, YAKUGAKU ZASSNI, J. PHARM. SOS. JAR., 1978, 98, NO 8, 10+
  作者：KAMETANI TETSUJI、 KIGASAWARA KAZUO、 HIIRAGI MINEHARU、 WAKISAKA KIKUO、 HAG+

  DOI：——

  日期：——