(R)-3-氨基-2-氧杂环酮对甲苯磺酸 | 149572-97-4

• 物质功能分类: 有机原料 - 氨基化合物 - 磺酸类氨基化合物
• 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
• 中文名称: (R)-3-氨基-2-氧杂环酮对甲苯磺酸
• 中文别名: (3R)-3-氨基-2-氧杂环丁酮对甲苯磺酸盐
• 英文名称: (R)-2-oxo-3-oxetanylammonium toluene-4-sulfonate
• 英文别名: (R)-3-aminooxetan-2-one 4-methylbenzenesulfonate；(3R)-3-aminooxetan-2-one;4-methylbenzenesulfonic acid
• CAS: 149572-97-4
• 化学式: C₃H₅NO₂*C₇H₈O₃S
• 分子量: 259.283
• InChiKey: AHPNSUJOZQROEQ-ARGLLVQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.11
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2932209090

反应信息

• 作为反应物：
  描述：

  (R)-3-氨基-2-氧杂环酮对甲苯磺酸 、 2-萘甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以20%的产率得到(R)-N-(2-oxo-3-oxetanyl)-2-naphthamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

  摘要：

  The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-alpha, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a, a series of beta-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC(50) = 420 nM; 7h, IC(50) = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo.

  DOI：

  10.1021/jm100582w
• 作为产物：
  描述：

  N-叔丁氧羰基-D-丝氨酸(Β-内酯) 、 对甲苯磺酸 在 三氟乙酸 作用下， 反应 0.25h， 以77%的产率得到(R)-3-氨基-2-氧杂环酮对甲苯磺酸
  参考文献：
  名称：

  手性1-（2'-氨基-2'-羧乙基）-1,4-二氢-6,7-喹喔啉-2,3-二酮的合成：α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体激动剂和拮抗剂。

  摘要：

  最近发现的6,7-二取代喹喔啉-2,3-二酮1可以拮抗对α-氨基-3-羟基-5-羟基-4-甲基-4-异恶唑丙酸酯（AMPA）和海藻酸的特异性结合和功能响应。尽管各种研究已经分析了在6和7位具有各种取代基的喹喔啉-2,3-二酮的活性，但是关于N取代作用的信息很少。从1（R1 = R2 = H）。该化合物抑制特异性的[3H] AMPA结合，但不抑制[3H]海藻酸酯结合。QXAA，AMPA和DNQX的IC50值分别为0.69、0.012和0.74 microM。R-和S-对映异构体通过不对称合成制备。S-异构体（2b）在结合测定中的效力比R-异构体（2d）高160倍，IC50值分别为0.23和38 microM。在功能测定中，两种对映异构体都是激动剂，S-异构体的EC50值为3 microM，而R-异构体的EC50值大于1 mM。在6和7位（2a和2c）处的甲基取代导致拮抗剂化合物，其特征在于S

  DOI：

  10.1021/jm950632+

文献信息

• Synthesis of Chiral 1-(2‘-Amino-2‘-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones:  α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate Receptor Agonists and Antagonists
  作者：Guoping Sun、Norman J. Uretsky、Lane J. Wallace、Gamal Shams、David M. Weinstein、Duane D. Miller

  DOI：10.1021/jm950632+

  日期：1996.1.1

  A racemic mixture of 1-(2'-amino-2'-carboxyethyl)-1,4-dihydroquinoxaline-2, 3-dione (QXAA, 2, R1 = R2 = H) has been synthesized from 1 (R1 = R2 = H). This compound inhibited specific [3H]AMPA binding but not [3H]kainate binding. IC50 values for QXAA, AMPA, and DNQX were 0.69, 0.012, and 0.74 microM, respectively. The R- and S-enantiomers were prepared by asymmetric synthesis. The S-isomer (2b) was 160-fold

  最近发现的6,7-二取代喹喔啉-2,3-二酮1可以拮抗对α-氨基-3-羟基-5-羟基-4-甲基-4-异恶唑丙酸酯（AMPA）和海藻酸的特异性结合和功能响应。尽管各种研究已经分析了在6和7位具有各种取代基的喹喔啉-2,3-二酮的活性，但是关于N取代作用的信息很少。从1（R1 = R2 = H）。该化合物抑制特异性的[3H] AMPA结合，但不抑制[3H]海藻酸酯结合。QXAA，AMPA和DNQX的IC50值分别为0.69、0.012和0.74 microM。R-和S-对映异构体通过不对称合成制备。S-异构体（2b）在结合测定中的效力比R-异构体（2d）高160倍，IC50值分别为0.23和38 microM。在功能测定中，两种对映异构体都是激动剂，S-异构体的EC50值为3 microM，而R-异构体的EC50值大于1 mM。在6和7位（2a和2c）处的甲基取代导致拮抗剂化合物，其特征在于S
• Enterobactin and Enantioenterobactin
  作者：Eric R. Marinez、Eric K. Salmassian、Thomas T. Lau、Carlos G. Gutierrez

  DOI：10.1021/jo9520194

  日期：1996.1.1
• Synthesis and Structure−Activity Relationships of <i>N</i>-(2-Oxo-3-oxetanyl)amides as <i>N</i>-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors
  作者：Carlos Solorzano、Francesca Antonietti、Andrea Duranti、Andrea Tontini、Silvia Rivara、Alessio Lodola、Federica Vacondio、Giorgio Tarzia、Daniele Piomelli、Marco Mor

  DOI：10.1021/jm100582w

  日期：2010.8.12

  The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-alpha, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a, a series of beta-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC(50) = 420 nM; 7h, IC(50) = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo.
• <i>N</i>-(2-Oxo-3-oxetanyl)carbamic Acid Esters as <i>N</i>-Acylethanolamine Acid Amidase Inhibitors: Synthesis and Structure–Activity and Structure–Property Relationships
  作者：Andrea Duranti、Andrea Tontini、Francesca Antonietti、Federica Vacondio、Alessandro Fioni、Claudia Silva、Alessio Lodola、Silvia Rivara、Carlos Solorzano、Daniele Piomelli、Giorgio Tarzia、Marco Mor

  DOI：10.1021/jm300349j

  日期：2012.5.24

  known and new β-lactone derivatives, focusing on the new class of N-(2-oxo-3-oxetanyl)carbamates. Replacement of the amide group with a carbamate one led to different stereoselectivity for NAAA inhibition and higher intrinsic stability, because of the reduced level of intramolecular attack at the lactone ring. The introduction of a syn methyl at the β-position of the lactone further improved chemical

  N-（2-氧代-3-氧杂环丁烷基）酰胺的β-内酯环是一类具有抗炎特性的N-酰基乙醇胺酸酰胺酶（NAAA）抑制剂，既可抑制NAAA，又可降低化合物的稳定性。在这里，我们研究了一组已知的和新的β-内酯衍生物的结构-活性和结构-性质之间的关系，重点研究了新型的N-（2-oxo-3-oxetanyl）carbamates。用氨基甲酸酯取代酰胺基团导致对NAAA抑制不同的立体选择性和更高的固有稳定性，因为内酯环上分子内攻击的水平降低了。在内酯的β-位引入顺甲基进一步改善了化学稳定性。一种侧链中的叔丁基取代基降低了与牛血清白蛋白的反应性。（2 S，3 R）-2-甲基-4-氧代-3-氧杂环丁烷基氨基甲酸5-苯基戊酯（27，URB913 / ARN077）具有良好的体外效价（IC 50 = 127 nM）抑制NAAA并显示出改善的稳定性。它在血浆中迅速裂解，从而支持其在局部应用中的使用。