3-Bromoisoxazole-5-carboxamide | 1241897-93-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-Bromoisoxazole-5-carboxamide
• 英文别名: 3-bromo-1,2-oxazole-5-carboxamide
• CAS: 1241897-93-7
• 化学式: C₄H₃BrN₂O₂
• 分子量: 190.984
• InChiKey: NEASCPSKJDUEKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Bromoisoxazole-5-carboxamide 在 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 为溶剂， 以97%的产率得到3-Bromoisoxazole-5-carbonitrile
  参考文献：
  名称：

  Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245

  摘要：

  A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.

  DOI：

  10.1021/op200186d
• 作为产物：
  描述：

  3-溴异恶唑-5-甲酸乙酯 在 氨 作用下， 以 甲醇 为溶剂， 以100%的产率得到3-Bromoisoxazole-5-carboxamide
  参考文献：
  名称：

  Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245

  摘要：

  A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.

  DOI：

  10.1021/op200186d

文献信息

• Design and Structure–Activity Relationships of Isothiocyanates as Potent and Selective <i>N</i>-Acylethanolamine-Hydrolyzing Acid Amidase Inhibitors
  作者：Michael S. Malamas、Spiro Pavlopoulos、Shakiru O. Alapafuja、Shrouq I. Farah、Alexander Zvonok、Khadijah A. Mohammad、Jay West、Nicholas Thomas Perry、Dimitrios N. Pelekoudas、Girija Rajarshi、Christina Shields、Honrao Chandrashekhar、Jodi Wood、Alexandros Makriyannis

  DOI：10.1021/acs.jmedchem.1c00076

  日期：2021.5.13

  of inflammatory and pain processes. The synthesis and structure-activity relationship studies encompassing the isothiocyanate pharmacophore have produced potent low nanomolar inhibitors for hNAAA, while exhibiting high selectivity (>100-fold) against other serine hydrolases and cysteine peptidases. We have followed a target-based structure–activity relationship approach, supported by computational methods

  N-酰基乙醇胺是信号脂质分子，参与与炎症和疼痛相关的病理生理状况。N-乙酰乙醇胺酸酰胺酶（NAAA）有利地水解脂质棕榈酰乙醇酰胺，其在调节炎症和疼痛过程中起关键作用。涉及异硫氰酸酯药效团的合成和构效关系研究已经产生了针对hNAAA的有效的低纳摩尔抑制剂，同时对其他丝氨酸水解酶和半胱氨酸肽酶表现出高选择性（> 100倍）。我们遵循了基于目标的结构-活性关系方法，并得到了计算方法和hNAAA的已知共晶的支持。我们已经鉴定出具有良好血浆稳定性的全身活性抑制剂（t1/2 > 2 h）和微粒体稳定性（t 1 /2〜15–30 min）作为研究NAAA在炎症，疼痛和药物成瘾中的作用的药理学工具。
• Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245
  作者：Mélina Girardin、Sarah J. Dolman、Sophie Lauzon、Stéphane G. Ouellet、Greg Hughes、Paul Fernandez、George Zhou、Paul D. O’Shea

  DOI：10.1021/op200186d

  日期：2011.9.16

  A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.