((R)-3-bromo-4,5-dihydroisoxazol-5-yl)methanamine | 143005-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: ((R)-3-bromo-4,5-dihydroisoxazol-5-yl)methanamine
• 英文别名: (R)-(3-bromo-4,5-dihydroisoxazol-5-yl)methanamine；(R)-3-bromo-5-aminomethyl-4,5-dihydroisoxazole；[(5R)-3-bromo-4,5-dihydro-1,2-oxazol-5-yl]methanamine
• CAS: 143005-81-6
• 化学式: C₄H₇BrN₂O
• 分子量: 179.016
• InChiKey: JLOLOZBWSBAUHW-GSVOUGTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-苄氧羰基-L-酪氨酸 、 ((R)-3-bromo-4,5-dihydroisoxazol-5-yl)methanamine 在 N-甲基吗啉 、 氢氧化钾 、 氯甲酸异丁酯 作用下， 生成 benzyl (S)-1-(((R)-3-bromo-4,5-dihydroisoxazol-5-yl)methylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-ylcarbamate
  参考文献：
  名称：

  Bromonitrile oxide [3+2] cycloadditions in water

  摘要：

  Bromonitrite oxide can be generated homogeneously in water at acidic pH, allowing efficient [3 + 2] cycloaddition with water soluble olefins and acetylenes. Allylammonium salts react with high regioselectivity and without the need for N-group protection.

  DOI：

  10.1016/s0040-4039(00)79827-3
• 作为产物：
  描述：

  (R)-5-(azidomethyl)-3-bromo-4,5-dihydroisoxazole 在 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以64%的产率得到((R)-3-bromo-4,5-dihydroisoxazol-5-yl)methanamine
  参考文献：
  名称：

  开发具有3-溴异恶唑啉战斗部的罗得沙星抑制剂

  摘要：

  通过将对映体纯的3-溴异恶唑啉战斗部与特定的拟肽识别部分相结合，可获得新型的罗德萨因抑制剂。所有衍生物均表现为罗得沙星的抑制剂，其微摩尔K i值低。发现它们对酶的活性与体外抗锥虫活性平行，IC 50值在中微摩尔范围内。值得注意的是，观察到寄生虫优于人蛋白酶，特别是组织蛋白酶B和L。

  DOI：

  10.1002/cmdc.201300390

文献信息

• Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors
  作者：Roberta Ettari、Santo Previti、Sandro Cosconati、Jochen Kesselring、Tanja Schirmeister、Silvana Grasso、Maria Zappalà

  DOI：10.3109/14756366.2015.1108972

  日期：2016.11.1

  Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar

  通过将对映体纯的3-溴异恶唑啉战斗部与作为特定识别部分的1,4-苯并二氮杂sc骨架相结合，开发出了新型罗得沙因抑制剂。事实证明，所有化合物均能抑制罗得沙因，其Ki值在低微摩尔范围内。发现它们对罗德沙因的活性与体外抗锥虫活性有关，IC50值范围从最活跃的罗德沙因抑制剂（R，S，S）-3的中微摩尔值到低微摩尔值。由于所有化合物均被证明是人组织蛋白酶L的弱抑制剂，因此所有化合物均对目标酶具有良好的选择性。
• Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles
  作者：R. Edward Watts、Mathew Siegel、Chaitan Khosla

  DOI：10.1021/jm060839a

  日期：2006.12.1

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.