2-{6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl}pyridine | 1110542-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-{6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl}pyridine
• 英文别名: 6-chloro-3-pyridin-2-yl-[1,2,4]triazolo[4,3-b]pyridazine
• CAS: 1110542-95-4
• 化学式: C₁₀H₆ClN₅
• 分子量: 231.644
• InChiKey: MVJZVTGJTQYPRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl}pyridine 、 3-(三氟甲基)苯硫酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-Pyridin-2-yl-6-[3-(trifluoromethyl)phenyl]sulfanyl-[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  Triazolopyridazine LRRK2 kinase inhibitors

  摘要：

  Leucine-rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson's disease (PD). Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD. Herein we report the discovery of a series of [1,2,4]triazolo[4,3-b]pyridazines that are potent against both wild-type and mutant LRRK2 kinase activity in biochemical assays and show an unprecedented selectivity towards the G2019S mutant. A structural rational for the observed selectivity is proposed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.043
• 作为产物：
  描述：

  生成 2-{6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl}pyridine
  参考文献：
  名称：

  Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold

  摘要：

  Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharmacological profiling of potent and highly selective kinase inhibitors based on a triazolopyridazine chemical scaffold. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.07.052

文献信息

• MAOS protocols for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines
  作者：Leslie N. Aldrich、Evan P. Lebois、L. Michelle Lewis、Natalia T. Nalywajko、Colleen M. Niswender、C. David Weaver、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.tetlet.2008.10.127

  日期：2009.1

  General, high-yielding MAOS protocols for the expedient synthesis of functionalized 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines are described amenable to an iterative analog library synthesis strategy for the lead optimization of an M1 antagonist screening hit. Optimized compounds proved to be highly selective M1 antagonists.

  描述了用于功能化 3,6-二取代-[1,2,4] 三唑并 [4,3- b ] 哒嗪的便利合成的通用、高产 MAOS 协议，该协议适用于先导优化的迭代类似物库合成策略M1 拮抗剂筛选命中。经优化的化合物被证明是高度选择性的 M1 拮抗剂。