6-chloro-3-cyclopropyl-[1,2,4]triazolo[4,3-b]pyridazine | 1152552-07-2

• 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-chloro-3-cyclopropyl-[1,2,4]triazolo[4,3-b]pyridazine
• CAS: 1152552-07-2
• 化学式: C₈H₇ClN₄
• mdl: MFCD11103598
• 分子量: 194.623
• InChiKey: VJYULOBBCNCMJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(三氟甲基)苯硫酚 、 6-chloro-3-cyclopropyl-[1,2,4]triazolo[4,3-b]pyridazine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-Cyclopropyl-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：

  N'-(6-chloropyridazin-3-yl)cyclopropanecarbohydrazide 在 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 0.5h， 以170 mg的产率得到6-chloro-3-cyclopropyl-[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  [EN] COMPOUNDS AND THEIR METHODS OF USE
  [FR] COMPOSÉS ET PROCÉDÉS D'UTILISATION DESDITS COMPOSÉS

  摘要：

  本发明部分涉及融合的杂环化合物和组合物，用于预防和/或治疗与电压门控钠离子通道异常功能相关的疾病或症状，例如异常的晚期/持续性钠电流。本文还提供了治疗与钠离子通道异常功能相关的疾病或症状，包括德拉维特综合征或癫痫的方法。

  公开号：

  WO2018098499A1

文献信息

• A Convenient One-Pot Synthesis of Triazolopyridine and Related Heterocycle Fused-Triazole Analogs Through Copper Catalyzed Oxidative Cyclization Strategy
  作者：R. Srinivasan、J. Sembian Ruso、N. S. Nagarajan、R. Senthil Kumaran、G. Manickam

  DOI：10.1002/jhet.2331

  日期：2016.3

  One‐pot synthesis of heterocycle fused‐triazole analogs from the corresponding aldehydes and heteroarylhydrazines is demonstrated. Transformation of hydrazones to the desired systems was achieved by employing the oxidative cyclization with catalytic CuBr2 and oxone. This reaction condition is mild and selective, and a wide range of functional groups were able to sustain. An array of biologically important

  证明了从相应的醛和杂芳基肼一锅法合成杂环稠合三唑类似物。通过使用催化性的CuBr 2和氧杂环丁烷进行氧化环化，可将转化为所需的系统。该反应条件温和且选择性，并且能够维持多种官能团。以相当高的产率获得了一系列生物学上重要的三唑并吡啶，三唑并哒嗪，三唑并嘧啶和三唑并喹啉。
• Discovery and optimization of cyclohexane-1,4-diamines as allosteric MALT1 inhibitors
  作者：Stefan Schiesser、Peter Hajek、Huw E. Pople、Helena Käck、Linda Öster、Rhona J. Cox

  DOI：10.1016/j.ejmech.2021.113925

  日期：2022.1

  discovery and optimization of (1s,4s)-N,N′-diaryl cyclohexane-1,4-diamines, a novel series of allosteric MALT1 inhibitors, resulting in compound 8 with single digit micromolar cell potency. X-ray analysis confirms that this compound binds to an induced allosteric site in MALT1. Compound 8 is highly selective and has an excellent in vivo rat PK profile with low clearance and high oral bioavailability, making

  抑制粘膜相关淋巴组织淋巴瘤易位蛋白-1 (MALT1) 是调节 NF-κB 信号传导的有前景的策略，具有治疗 B 细胞淋巴瘤和自身免疫性疾病的潜力。我们描述了 (1 s ,4 s ) -N , N' -二芳基环己烷-1,4-二胺的发现和优化，这是一系列新的变构 MALT1 抑制剂，导致化合物8具有个位数的微摩尔细胞效力。X 射线分析证实该化合物与 MALT1 中的诱导变构位点结合。化合物8具有高选择性，具有优异的体内具有低清除率和高口服生物利用度的大鼠 PK 曲线，使其成为进一步优化的有希望的先导。
• Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold
  作者：Paul Galatsis、Jaclyn L. Henderson、Bethany L. Kormos、Seungil Han、Ravi G. Kurumbail、Travis T. Wager、Patrick R. Verhoest、G. Stephen Noell、Yi Chen、Elie Needle、Zdenek Berger、Stefanus J. Steyn、Christopher Houle、Warren D. Hirst

  DOI：10.1016/j.bmcl.2014.07.052

  日期：2014.9

  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.
• COMPOUNDS AND THEIR METHODS OF USE
  申请人：Praxis Precision Medicines, Inc.

  公开号：US20210188852A1

  公开（公告）日：2021-06-24

  The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.