2-bis(tert-butyloxycarbonyl)aminoimidazole | 1227833-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-bis(tert-butyloxycarbonyl)aminoimidazole
• 英文别名: tert-Butyl N-[(tert-butoxy)carbonyl]-N-(1H-imidazol-2-yl)carbamate；tert-butyl N-(1H-imidazol-2-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate
• CAS: 1227833-98-8
• 化学式: C₁₃H₂₁N₃O₄
• 分子量: 283.327
• InChiKey: PVCIOHPJJHBADJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-bis(tert-butyloxycarbonyl)aminoimidazole 、 (S)-1-tert-butyl-2-[bis(tert-butoxycarbonyl)amino]-5-bromopentanoate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到2-[bis(tert-butyloxycarbonyl)amino]-5-[2-bis(tert-butyloxycarbonyl)aminoimidazol-1-yl]pentanoic acid tert-butyl ester
  参考文献：
  名称：

  2-Aminoimidazole Amino Acids as Inhibitors of the Binuclear Manganese Metalloenzyme Human Arginase I

  摘要：

  Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant L-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (AlP, 10), binds to human arginase I with K-d = 2 mu M and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.

  DOI：

  10.1021/jm100306a
• 作为产物：
  描述：

  2-bis(tert-butyloxycarbonyl)amino-1-tert-butyloxycarbonylimidazole 在 氨 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以56%的产率得到2-bis(tert-butyloxycarbonyl)aminoimidazole
  参考文献：
  名称：

  2-Aminoimidazole Amino Acids as Inhibitors of the Binuclear Manganese Metalloenzyme Human Arginase I

  摘要：

  Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant L-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (AlP, 10), binds to human arginase I with K-d = 2 mu M and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.

  DOI：

  10.1021/jm100306a

文献信息

• 2-Aminoimidazole Amino Acids as Inhibitors of the Binuclear Manganese Metalloenzyme Human Arginase I
  作者：Monica Ilies、Luigi Di Costanzo、Michelle L. North、Jeremy A. Scott、David W. Christianson

  DOI：10.1021/jm100306a

  日期：2010.5.27

  Arginase, a key metalloenzyme of the urea cycle that converts L-arginine into L-ornithine and urea, is presently considered a pharmaceutical target for the management of diseases associated with aberrant L-arginine homeostasis, such as asthma, cardiovascular diseases, and erectile dysfunction. We now report the design, synthesis, and evaluation of a series of 2-aminoimidazole amino acid inhibitors in which the 2-aminoimidazole moiety serves as a guanidine mimetic. These compounds represent a new class of arginase inhibitors. The most potent inhibitor identified in this study, 2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid (AlP, 10), binds to human arginase I with K-d = 2 mu M and significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation. These findings suggest that 2-aminoimidazole amino acids represent new leads for the development of arginase inhibitors with promising pharmacological profiles.