5-氮杂环丁烷-3-基-3-苯基-1,2,4-噁二唑盐酸盐 | 1351654-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-氮杂环丁烷-3-基-3-苯基-1,2,4-噁二唑盐酸盐
• 英文名称: 5-(azetidin-3-yl)-3-phenyl-1,2,4-oxadiazole hydrochloride
• 英文别名: 5-Azetidin-3-yl-3-phenyl-1,2,4-oxadiazole hydrochloride；5-(azetidin-3-yl)-3-phenyl-1,2,4-oxadiazole;hydrochloride
• CAS: 1351654-21-1
• 化学式: C₁₁H₁₁N₃O*ClH
• 分子量: 237.689
• InChiKey: GSMGRPISFJYCHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.85
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  51
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氮杂环丁烷-3-基-3-苯基-1,2,4-噁二唑盐酸盐 、 (+)-(1S,2S,4R)-bicyclo<2.2.1>heptane-2-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 [(1S,2S,4R)-2-bicyclo[2.2.1]heptanyl]-[3-(3-phenyl-1,2,4-oxadiazol-5-yl)azetidin-1-yl]methanone
  参考文献：
  名称：

  Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators

  摘要：

  A novel series of aryl azetidinyl oxadiazoles are identified as mGluR5 positive allosteric modulators (PAMs) with improved physico-chemical properties. N-substituted cyclohexyl and exo-norbornyl carboxamides, and carbamate analogs of azetidines are moderate to potent mGluR5 PAMs. The aryl, lower alkyl carboxamides analogs and sulfonamide analogs of azetidines are moderate mGluR5 negative allosteric modulators (NAMs). In the aryl oxadiazole moiety, substituents such as fluoro, chloro and methyl are well tolerated at the meta position while para substituents led to either inactive compounds or NAMs. A tight pharmacophore and subtle 'PAM to NAM switching' with close analogs makes the optimization of the series extremely challenging. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.044
• 作为产物：
  描述：

  苯甲酰胺肟 在 盐酸 、 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 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 5-氮杂环丁烷-3-基-3-苯基-1,2,4-噁二唑盐酸盐
  参考文献：
  名称：

  发现 4-(1,2,4-Oxadiazol-5-yl)azepan-2-one 衍生物作为一类新的大麻素 2 型受体激动剂用于治疗炎症性疼痛

  摘要：

  选择性地靶向大麻素受体 CB2 是一种有吸引力的治疗策略，用于治疗炎症性疼痛，而没有大麻素受体 CB1 介导的精神副作用。在此，我们报告发现 4-(1,2,4-oxadiazol-5-yl)azepan-2-one 衍生物作为一类新的 CB2 激动剂。系统的构效关系研究导致鉴定出最有效的化合物25r。该化合物显示出 CB2 对 CB1 的高选择性（CB2 EC 50 = 21.0 nM，E max = 87%，CB1 EC 50 > 30 μM，比率 CB1/CB2 > 1428），具有良好的药代动力学特性。特别是，25r在啮齿动物炎症性疼痛的镇痛模型中显示出显着的疗效。所有结果表明，化合物25r可以作为治疗炎症性疼痛的先导化合物，值得进一步深入研究。

  DOI：

  10.1021/acs.jmedchem.2c01943

文献信息

• Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase
  作者：Christopher R. Butler、Elizabeth M. Beck、Anthony Harris、Zhen Huang、Laura A. McAllister、Christopher W. am Ende、Kimberly Fennell、Timothy L. Foley、Kari Fonseca、Steven J. Hawrylik、Douglas S. Johnson、John D. Knafels、Scot Mente、G. Stephen Noell、Jayvardhan Pandit、Tracy B. Phillips、Justin R. Piro、Bruce N. Rogers、Tarek A. Samad、Jane Wang、Shuangyi Wan、Michael A. Brodney

  DOI：10.1021/acs.jmedchem.7b01531

  日期：2017.12.14

  Monoacylglycerol lipase (MAGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the CNS. MAGL catalyzes the conversion of 2-AG to arachidonic acid (AA), a precursor to the proinflammatory eicosannoids such as prostaglandins. Herein we describe highly efficient MAGL inhibitors, identified through a parallel medicinal chemistry approach that highlighted the improved efficiency of azetidine and piperidine-derived carbamates. The discovery and optimization of 3-substituted azetidine carbamate irreversible inhibitors of MAGL were aided by the generation of inhibitor-bound MAGL crystal structures. Compound 6, a highly efficient and selective MAGL inhibitor against recombinant enzyme and in a cellular context, was tested in vivo and shown to elevate central 2-AG levels at a 10 mg/kg dose.
• Azetidinyl oxadiazoles as potent mGluR5 positive allosteric modulators
  作者：Mathivanan Packiarajan、Christine G. Mazza Ferreira、Sang-Phyo Hong、Andrew D. White、Gamini Chandrasena、Xiaosui Pu、Robbin M. Brodbeck、Albert J. Robichaud

  DOI：10.1016/j.bmcl.2012.08.044

  日期：2012.10

  A novel series of aryl azetidinyl oxadiazoles are identified as mGluR5 positive allosteric modulators (PAMs) with improved physico-chemical properties. N-substituted cyclohexyl and exo-norbornyl carboxamides, and carbamate analogs of azetidines are moderate to potent mGluR5 PAMs. The aryl, lower alkyl carboxamides analogs and sulfonamide analogs of azetidines are moderate mGluR5 negative allosteric modulators (NAMs). In the aryl oxadiazole moiety, substituents such as fluoro, chloro and methyl are well tolerated at the meta position while para substituents led to either inactive compounds or NAMs. A tight pharmacophore and subtle 'PAM to NAM switching' with close analogs makes the optimization of the series extremely challenging. (c) 2012 Elsevier Ltd. All rights reserved.
• Discovery of 4-(1,2,4-Oxadiazol-5-yl)azepan-2-one Derivatives as a New Class of Cannabinoid Type 2 Receptor Agonists for the Treatment of Inflammatory Pain
  作者：Jinshan Nan、Jingming Liu、Guifeng Lin、Shanshan Zhang、Anjie Xia、Pei Zhou、Yangli Zhou、Jiahao Zhang、Jinlong Zhao、Shiyu Zhang、Chong Huang、Yifei Wang、Qian Hu、Junxian Chen、Mingli Xiang、Xin Yang、Shengyong Yang

  DOI：10.1021/acs.jmedchem.2c01943

  日期：2023.3.9

  attractive therapeutic strategy for the treatment of inflammatory pain without psychiatric side effects mediated by the cannabinoid receptor CB1. Herein, we report the discovery of 4-(1,2,4-oxadiazol-5-yl)azepan-2-one derivatives as a new class of CB2 agonists. Systematic structure–activity relationship investigations resulted in the identification of the most potent compound 25r. This compound displayed high

  选择性地靶向大麻素受体 CB2 是一种有吸引力的治疗策略，用于治疗炎症性疼痛，而没有大麻素受体 CB1 介导的精神副作用。在此，我们报告发现 4-(1,2,4-oxadiazol-5-yl)azepan-2-one 衍生物作为一类新的 CB2 激动剂。系统的构效关系研究导致鉴定出最有效的化合物25r。该化合物显示出 CB2 对 CB1 的高选择性（CB2 EC 50 = 21.0 nM，E max = 87%，CB1 EC 50 > 30 μM，比率 CB1/CB2 > 1428），具有良好的药代动力学特性。特别是，25r在啮齿动物炎症性疼痛的镇痛模型中显示出显着的疗效。所有结果表明，化合物25r可以作为治疗炎症性疼痛的先导化合物，值得进一步深入研究。