6-methyl-5H-[1,2,4]triazolo[4,3-b]pyridazin-8-one | 18591-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并哒嗪类
• 英文名称: 6-methyl-5H-[1,2,4]triazolo[4,3-b]pyridazin-8-one
• 英文别名: 8-Hydroxy-6-methyl-s-triazolo<4,3-b>pyridazin；8-hydroxy-6-methyl-[1,2,4]triazolo[4,3-b]pyridazine；6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ol；6-methyl-7H-[1,2,4]triazolo[4,3-b]pyridazin-8-one；6-Methyl-8-hydroxy-s-triazolo<4,3-b>pyridazin；6-Methyl-8-hydroxy-s-triazolopyridazin
• CAS: 18591-70-3
• 化学式: C₆H₆N₄O
• 分子量: 150.14
• InChiKey: PQKCWHQSKRXSPN-UHFFFAOYSA-N

物化性质

• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.14
• 重原子数：
  11.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  6-methyl-5H-[1,2,4]triazolo[4,3-b]pyridazin-8-one 在 三氯氧磷 作用下， 以79.5%的产率得到8-chloro-6-methyl-[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  含杂芳基酰胺结构的三唑并杂环类化合物的制备及应用

  摘要：

  本发明公开了一种含杂芳基酰胺结构的三唑并杂环类化合物、其几何异构体及其药学上可接受的盐、水合物、溶剂化物或前药。本发明含杂芳基酰胺结构的三唑并杂环类化合物，及其药学上可接受的盐、水合物或溶剂化物作为活性成份，与药学上可接受的载体或赋型剂混合制备成组合物，并制备成临床上可接受的剂型。本发明化合物具有强的抑制c‑Met激酶的作用，且对EGFR显示出较好的抑制活性，在制备治疗由于c‑Met、EGFR激酶异常高表达所引起疾病的药物中的应用，特别是在制备治疗和/或预防癌症的药物中的应用。

  公开号：

  CN110407839B
• 作为产物：
  描述：

  7-diazo-6-methyl-7H-[1,2,4]triazolo[4,3-b]pyridazin-8-one 生成 6-methyl-5H-[1,2,4]triazolo[4,3-b]pyridazin-8-one
  参考文献：
  名称：

  STANOVNIK B.; TISLER M.; KIRN B.; KOVAC I., J. HETEROCYCL. CHEM., 1979, 16, NO 1, 195-198

  摘要：

  DOI：

文献信息

• 含杂芳基酰胺结构的三唑并杂环类化合物的制备及应用
  申请人：江西科技师范大学

  公开号：CN110407839B

  公开（公告）日：2022-01-04

  本发明公开了一种含杂芳基酰胺结构的三唑并杂环类化合物、其几何异构体及其药学上可接受的盐、水合物、溶剂化物或前药。本发明含杂芳基酰胺结构的三唑并杂环类化合物，及其药学上可接受的盐、水合物或溶剂化物作为活性成份，与药学上可接受的载体或赋型剂混合制备成组合物，并制备成临床上可接受的剂型。本发明化合物具有强的抑制c‑Met激酶的作用，且对EGFR显示出较好的抑制活性，在制备治疗由于c‑Met、EGFR激酶异常高表达所引起疾病的药物中的应用，特别是在制备治疗和/或预防癌症的药物中的应用。
• Bioisosteric Transformations and Permutations in the Triazolopyrimidine Scaffold To Identify the Minimum Pharmacophore Required for Inhibitory Activity against <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase
  作者：Alka Marwaha、John White、Farah El_Mazouni、Sharon A Creason、Sreekanth Kokkonda、Frederick S. Buckner、Susan A. Charman、Margaret A. Phillips、Pradipsinh K. Rathod

  DOI：10.1021/jm300351w

  日期：2012.9.13

  Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P. falciparum dihydroorotate dehydrogenase that inhibit parasite in vitro growth with similar activity. Lead optimization of this series led to the recent identification of a preclinical candidate, showing good activity against P. falciparum in mice. As part of a backup program around this scaffold, we explored heteroatom rearrangement and substitution in the triazolopyrimidine ring and have identified several other ring configurations that are active as PfDHODH inhibitors. The imidazo[1,2-a]pyrimidines were shown to bind somewhat more potently than the triazolopyrimidines depending on the nature of the amino aniline substitution. DSM151, the best candidate in this series, binds with 4-fold better affinity (PfDHODH IC50 = 0.077 mu M) than the equivalent triazolopyrimidine and suppresses parasites in vivo in the Plasmodium berghei model.
• Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-<i>b</i>]pyridazin-8-amine Derivatives as Tankyrase Inhibitors
  作者：Paride Liscio、Andrea Carotti、Stefania Asciutti、Tobias Karlberg、Daniele Bellocchi、Laura Llacuna、Antonio Macchiarulo、Stuart A Aaronson、Herwig Schüler、Roberto Pellicciari、Emidio Camaioni

  DOI：10.1021/jm401356t

  日期：2014.3.27

  Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.
• STANOVNIK B.; TISLER M.; KIRN B.; KOVAC I., J. HETEROCYCL. CHEM., 1979, 16, NO 1, 195-198
  作者：STANOVNIK B.、 TISLER M.、 KIRN B.、 KOVAC I.

  DOI：——

  日期：——