N-(5-(4-(6-aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(5-(4-(6-aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide
• 英文别名: N-(5-(4-(6-aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyrazolo[1,5-a]pyridin-2-yl)acetamide；N-(5-(4-(6-Aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide；N-[5-[4-(6-aminopyridazin-3-yl)butyl]-1,3,4-thiadiazol-2-yl]-2-pyridin-2-ylacetamide
• 化学式: C₁₇H₁₉N₇OS
• 分子量: 369.45
• InChiKey: KYBNUYGFGWMOFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(5-(4-(6-aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide 在 copper(l) iodide 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成
  参考文献：
  名称：

  Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors

  摘要：

  Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b01035
• 作为产物：
  描述：

  N-(5-(4-(6-aminopyridazin-3-yl)but-3-yn-1-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide 在 氢气 、 镍 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以90 %的产率得到N-(5-(4-(6-aminopyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)acetamide
  参考文献：
  名称：

  谷氨酰胺酶别构位点共价抑制剂及其制备方法与应用

  摘要：

  本发明提供一种谷氨酰胺酶别构位点共价抑制剂及其的制备方法与应用。基于现有KGA别构位点抑制剂，设计合成含α，β‑不饱和羧酸酯侧链基团是常见共价抑制剂的片段的新型谷氨酰胺酶共价抑制剂，提高现有KGA别构位点抑制剂的谷氨酰胺酶抑制作用和抗肿瘤活性。本发明的共价抑制剂可以选择性的抑制KGA酶，其抑制肿瘤细胞生长的活性比先导化合物CB839提高了3倍以上。

  公开号：

  CN115286625A

文献信息

• [EN] HETEROCYCLIC INHIBITORS OF GLUTAMINASE<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE GLUTAMINASE
  申请人：CALITHERA BIOSCIENCES INC

  公开号：WO2013078123A1

  公开（公告）日：2013-05-30

  The invention relates to the heterocyclic compounds of Formula (I) as defined further herein, and pharmaceutical preparations thereof. The invention further relates to methods of treating cancer, immunological or neurological diseases using the heterocyclic compounds of the invention.

  本发明涉及式(I)定义的杂环化合物及其药物制剂。本发明进一步涉及使用本发明的杂环化合物治疗癌症、免疫性或神经疾病的方法。
• 谷氨酰胺酶小分子荧光探针及其制备方法和 用途
  申请人：中国药科大学

  公开号：CN110590801B

  公开（公告）日：2020-11-03

  本发明公开了具有通式(I)谷氨酰胺酶小分子荧光探针及其制备方法和用途。该类探针的结构模块包括：谷氨酰胺酶结合基团、连接链和荧光报告基团。本发明的谷氨酰胺酶小分子荧光探针可用于谷氨酰胺酶抑制剂的高通量筛选，指导谷氨酰胺酶抑制剂的发现及结构优化。以此类结构的探针作为工具分子，可以快速、准确地确证小分子化合物与靶标蛋白的结合情况。
• HETEROCYCLIC INHIBITORS OF GLUTAMINASE
  申请人：Calithera Biosciences Inc.

  公开号：US20130157998A1

  公开（公告）日：2013-06-20

  The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention.

  本发明涉及新型杂环化合物及其制药制剂。本发明还涉及使用所述新型杂环化合物治疗的方法。
• [EN] HETEROCYCLIC GLUTAMINASE INHIBITORS<br/>[FR] INHIBITEURS DE GLUTAMINASE HÉTÉROCYCLIQUES
  申请人：CALITHERA BIOSCIENCES INC

  公开号：WO2014078645A1

  公开（公告）日：2014-05-22

  Disclosed herein are heterocyclic compounds containing thiadiazole and/or pyridazine rings, as well as pharmaceutical preparations thereof. The compounds herein are further made known to be useful as glutaminase inhibitors with potential uses in treating cancer, immunological and neurological diseases.

  本文披露了含有噻二唑和/或吡嗪烷环的杂环化合物及其制药制剂。本文中的化合物进一步被认为是谷氨酰胺酶抑制剂，在治疗癌症、免疫和神经系统疾病方面具有潜在用途。
• TREATMENT OF CANCER WITH HETEROCYCLIC INHIBITORS OF GLUTAMINASE
  申请人：Calithera Biosciences, Inc.

  公开号：US20150004134A1

  公开（公告）日：2015-01-01

  The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.

  本发明涉及新型杂环化合物及其制药制剂。本发明还涉及使用所述新型杂环化合物治疗或预防癌症的方法。