6-(piperazin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine | 1204296-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(piperazin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine
• 英文别名: 1-{[1,2,4]Triazolo[4,3-b]pyridazin-6-yl}piperazine；6-piperazin-1-yl-[1,2,4]triazolo[4,3-b]pyridazine
• CAS: 1204296-27-4
• 化学式: C₉H₁₂N₆
• mdl: MFCD16652736
• 分子量: 204.234
• InChiKey: RZINTGMACQMYCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(piperazin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine 在 lithium hydroxide monohydrate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 18.5h， 生成 3-((4-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperazin-1-yl)sulfonyl)propanoic acid
  参考文献：
  名称：

  Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors

  摘要：

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.

  DOI：

  10.1021/acs.jmedchem.0c00949
• 作为产物：
  描述：

  6-氯-1,2,4-三唑并[4,3-b]哒嗪 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 42.0h， 生成 6-(piperazin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine
  参考文献：
  名称：

  Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors

  摘要：

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.

  DOI：

  10.1021/acs.jmedchem.0c00949

文献信息

• [EN] ARYLACETAMIDE ANALOGS OF PIPERAZINE-[1,2,4]TRIAZOLO[4,3-B]PYRIDAZINES<br/>[FR] ANALOGUES D'ARYLACÉTAMIDE DE PIPÉRAZINE-[1,2,4]TRIAZOLO [4,3-B]PYRIDAZINES
  申请人：UNIV OF VERMONT AND STATE AGRICULTURAL COLLEGE

  公开号：WO2021252505A1

  公开（公告）日：2021-12-16

  Provided are compounds with the following structure: Formula (I), and methods of making and using same. The methods of using the compounds may be methods for treating or prophylaxis of a cryptosporidium infection.

  提供以下结构的化合物：公式（I），以及制备和使用这些化合物的方法。使用这些化合物的方法可能是治疗或预防隐孢子虫感染的方法。
• Methods for treating cryptosporidiosis using triazolopyridazines
  申请人：University of Vermont and State Agricultural College

  公开号：US10363254B2

  公开（公告）日：2019-07-30

  Methods for treating or prophylaxis of a Cryptosporidium infection using compositions comprising a structure disclosed herein. Also provided are pharmaceutical compositions and kits for alleviating the symptoms of, for treating, or for preventing the occurrence of Cryptosporidium infection. The kits comprise one or more compounds having a structure disclosed herein, such as in an oral composition, and instructions for use, storage, and the like.

  使用包含本文公开的结构的组合物治疗或预防隐孢子虫感染的方法。还提供了用于缓解隐孢子虫感染症状、治疗或预防隐孢子虫感染发生的药物组合物和试剂盒。这些试剂盒包括一种或多种具有本文所公开结构的化合物，如口服组合物，以及使用、储存等说明。
• METHODS FOR TREATING CRYPTOSPORIDIOSIS USING TRIAZOLOPYRIDAZINES
  申请人：University of Vermont and State Agricultural College

  公开号：US20180064711A1

  公开（公告）日：2018-03-08

  Methods for treating or prophylaxis of a Cryptosporidium infection using compositions comprising a structure disclosed herein. Also provided are pharmaceutical compositions and kits for alleviating the symptoms of, for treating, or for preventing the occurrence of Cryptosporidium infection. The kits comprise one or more compounds having a structure disclosed herein, such as in an oral composition, and instructions for use, storage, and the like.
• [EN] METHODS FOR TREATING CRYPTOSPORIDIOSIS USING TRIAZOLOPYRIDAZINES<br/>[FR] MÉTHODES POUR LE TRAITEMENT DE LA CRYPTOSPORIDIOSE À L'AIDE DE TRIAZOLOPYRIDAZINES
  申请人：UNIV OF VERMONT AND STATE AGRICULTURAL COLLEGE

  公开号：WO2016161125A1

  公开（公告）日：2016-10-06

  Methods for treating or prophylaxis of a Cryptosporidium infection using compositions comprising a structure disclosed herein. Also provided are pharmaceutical compositions and kits for alleviating the symptoms of, for treating, or for preventing the occurrence of Cryptosporidium infection. The kits comprise one or more compounds having a structure disclosed herein, such as in an oral composition, and instructions for use, storage, and the like.
• Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
  作者：Markus Schade、Beatrix Merla、Bernhard Lesch、Markus Wagener、Simone Timmermanns、Katrien Pletinckx、Torsten Hertrampf

  DOI：10.1021/acs.jmedchem.0c00949

  日期：2020.10.22

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.