tert-butyl 4-(2-(4-bromophenoxy)acetyl)piperazine-1-carboxylate | 1147343-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(2-(4-bromophenoxy)acetyl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[2-(4-bromophenoxy)acetyl]piperazine-1-carboxylate
• CAS: 1147343-55-2
• 化学式: C₁₇H₂₃BrN₂O₄
• 分子量: 399.285
• InChiKey: DOCIQCPLGHAUGF-UHFFFAOYSA-N

物化性质

• 沸点：
  518.7±50.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(4-bromophenoxy)acetyl)piperazine-1-carboxylate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 2-(4-Bromophenoxy)-1-piperazin-1-ylethanone;hydrochloride
  参考文献：
  名称：

  Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma

  摘要：

  This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational-design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150X against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity. Therapeutic efficacy Of compound 7f in the clinically relevant aeroallergen-induced acute asthma model in mice provides a rationale for developing AMCase inhibitor for the treatment of asthma.

  DOI：

  10.1021/acs.jmedchem.7b01051
• 作为产物：
  描述：

  对溴苯氧乙酸 、 N-Boc-哌嗪 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到tert-butyl 4-(2-(4-bromophenoxy)acetyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma

  摘要：

  This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational-design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150X against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity. Therapeutic efficacy Of compound 7f in the clinically relevant aeroallergen-induced acute asthma model in mice provides a rationale for developing AMCase inhibitor for the treatment of asthma.

  DOI：

  10.1021/acs.jmedchem.7b01051

文献信息

• An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6]
  作者：Dengyou Zhang、Haifeng Sun、Lei Zhang、Yu Zhou、Chunpu Li、Hualiang Jiang、Kaixian Chen、Hong Liu

  DOI：10.1039/c2cc17468e

  日期：——

  A practical Pd(PPh3)4/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K4[Fe(CN)6] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh3)4 under mild and green conditions, even without the assistance of other ligands.

  一种用于合成具有药物相关性的氨基吡啶腈中间体的实用Pd(PPh3)4/DBU催化体系，以及其他多种使用无毒K4[Fe(CN)6]的芳基腈，已经开发出来。我们新方案中氰化的关键特点在于，反应可以在温和且环保的条件下，使用易于获得的Pd(PPh3)4进行，甚至无需其他配体的辅助。
• Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma
  作者：Marzena Mazur、Jacek Olczak、Sylwia Olejniczak、Robert Koralewski、Wojciech Czestkowski、Anna Jedrzejczak、Jakub Golab、Karolina Dzwonek、Barbara Dymek、Piotr L. Sklepkiewicz、Agnieszka Zagozdzon、Tom Noonan、Keyvan Mahboubi、Bruce Conway、Ryan Sheeler、Paul Beckett、William M. Hungerford、Alberto Podjarny、Andre Mitschler、Alexandra Cousido-Siah、Firas Fadel、Adam Golebiowski

  DOI：10.1021/acs.jmedchem.7b01051

  日期：2018.2.8

  This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational-design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150X against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity. Therapeutic efficacy Of compound 7f in the clinically relevant aeroallergen-induced acute asthma model in mice provides a rationale for developing AMCase inhibitor for the treatment of asthma.