[3-(2-hydroxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide hydrobromide | 959600-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [3-(2-hydroxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide hydrobromide
• 英文别名: 2-(2-Imino-4,5-dimethyl-thiazol-3-yl)-ethanol hydrobromide；2-(2-imino-4,5-dimethyl-1,3-thiazol-3-yl)ethanol;hydrobromide
• CAS: 959600-44-3
• 化学式: BrH*C₇H₁₂N₂OS
• 分子量: 253.163
• InChiKey: IPPXEEPJJVJJKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.22
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  72.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [3-(2-hydroxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide hydrobromide 在 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 20.08h， 生成 (Z)-N-(3-(2-(2-fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3H)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide
  参考文献：
  名称：

  Development of a High-Affinity PET Radioligand for Imaging Cannabinoid Subtype 2 Receptor

  摘要：

  Cannabinoid receptors type 2 (CB2) represent a target with increasing importance for neuroimaging due to its upregulation under various pathological conditions. Encouraged by preliminary results obtained with [C-11](Z)-N-(3- (2-methoxyethyl)-4,5-dimethylthiazol-2(3H)-ylidene)-2,2,3,3-tetramethyl-cyclopropanecarboxamide ([C-11]A-836339, [C-11]1) in a mouse model of acute neuroinflammation (induced by lipopolysaccharide, LPS), we designed a library of fluorinated analogs aiming for an [F-18]-labeled radiotracer with improved CB2 binding affinity and selectivity. Compound (Z)-N-(3-(4-fluorobutyl)-4,5-dimethylthiazol-2(3H)-ylidene)-2,2,3,3-tetramethyl-cyclopropanecarboxamide (29) was selected as a ligand with the highest CB2 affinity (K-i = 0.39 nM) and selectivity over CB1 (factor 1000). [F-18]29 was prepared starting from the bromo precursor (53). Specific binding was shown in vitro whereas fast metabolism was observed in vivo in CD-1 mice. Animal PET revealed a brain uptake comparable to [C-11]1. In the LPS treated mice, a 20-30% higher uptake in brain was found in comparison to non-treated mice (n = 3, P < 0.05).

  DOI：

  10.1021/acs.jmedchem.6b00554
• 作为产物：
  描述：

  2-氨基-4,5-二甲基噻唑 、 2-溴乙醇 以 neat (no solvent) 为溶剂， 生成 [3-(2-hydroxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide hydrobromide
  参考文献：
  名称：

  从噻唑衍生物的构效关系到对大麻素亚型2 PET成像的新型放射性示踪剂的体内评价

  摘要：

  大麻素2型受体（CB 2 R）的上调揭示了病理性疾病（例如癌症，疼痛或神经退行性疾病）的炎症过程。其中，CB 2 R激动剂A-836339已被碳11标记，用于CB 2 R的PET成像，并在阿尔茨海默氏病小鼠模型中显示出令人鼓舞的结果。本工作的目的是开发用于氟18标记的A-836339氟化类似物，以设计用于CB 2 R成像的新型PET示踪剂。通过两到三个步骤合成了七个A-836339氟化类似物，它们对人和小鼠CB 2的结合亲和力和选择性R及其早期ADME配置文件进行了测量。其中，化合物2f（K ihCB2R = 0.1 nM，K ihCB1R / K ihCB2R = 300）对CB 2 R表现出高亲和力和选择性，但还具有亲脂性，动力学溶解性和膜渗透性，因此被进一步选择用于体外代谢研究。用人或大鼠肝微粒体温育2f，然后进行LC / MS分析，发现存在六种不同的代谢产物，这些代谢产物主要是由氧

  DOI：

  10.1021/acs.molpharmaceut.7b00746

文献信息

• NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
  申请人：Florjancic S. Alan

  公开号：US20080064699A1

  公开（公告）日：2008-03-13

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R 1 , R 2 , R 3 , R 4 , and L 2 , are defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

  本发明涉及式（I）的化合物，或其药学上可接受的盐，前药，前药盐或其组合物，其中R1，R2，R3，R4和L2在规范中有定义，包括这些化合物的组合物，以及使用这些化合物和组合物治疗疾病和病症的方法。
• Compounds as cannabinoid receptor ligands and uses thereof
  申请人：Abbott Laboratories

  公开号：US07875639B2

  公开（公告）日：2011-01-25

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and L2, are defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

  本发明涉及公式（I）的化合物，或其药学上可接受的盐，前药，前药盐或其组合物，其中R1，R2，R3，R4和L2在规范中定义，包括这样的化合物的组合物，并使用这样的化合物和组合物治疗疾病和病症的方法。
• Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)
  作者：Andrew G. Horti、Yongjun Gao、Hayden T. Ravert、Paige Finley、Heather Valentine、Dean F. Wong、Christopher J. Endres、Alena V. Savonenko、Robert F. Dannals

  DOI：10.1016/j.bmc.2010.05.058

  日期：2010.7

  Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl3H- thiazol-(2Z)-ylidene] amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [C-11] A-836339 ([C-11] 1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [C-11] 1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [C-11] 1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with A beta amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB2 receptors binding in the neuroinflammation and related disorders can be measured in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
• COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
  申请人：AbbVie Inc.

  公开号：EP2024349B1

  公开（公告）日：2017-08-02
• US7875639B2
  申请人：——

  公开号：US7875639B2

  公开（公告）日：2011-01-25