2-甲基-2-丙基4-{[(4-溴苄基)氨基]甲基}-1-哌啶羧酸酯 | 887581-89-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 2-甲基-2-丙基4-{[(4-溴苄基)氨基]甲基}-1-哌啶羧酸酯
• 英文名称: tert-butyl 4-(((4-bromobenzyl)amino)methyl)piperidine-1-carboxylate
• 英文别名: 1-Boc-4-[(4-bromobenzylamino)methyl]piperidine；tert-butyl 4-[[(4-bromophenyl)methylamino]methyl]piperidine-1-carboxylate
• CAS: 887581-89-7
• 化学式: C₁₈H₂₇BrN₂O₂
• 分子量: 383.329
• InChiKey: XDSQZLPJMGQUOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基4-{[(4-溴苄基)氨基]甲基}-1-哌啶羧酸酯 在 盐酸 、 三乙酰氧基硼氢化钠 、 potassium carbonate 作用下， 以 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 6.0h， 生成 5-(4-(((4-bromobenzyl)(methyl)amino)methyl)piperidin-1-yl)-1H-1,2,4-triazol-3-amine trihydrochloride
  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：

  对溴苯甲醛 、 1-叔丁氧羰基-4-氨甲基哌啶 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 2-甲基-2-丙基4-{[(4-溴苄基)氨基]甲基}-1-哌啶羧酸酯
  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

• SUBSTITUTED AMINO TRIAZOLES, AND METHODS USING SAME
  申请人：Institute for Drug Discovery, LLC

  公开号：EP3082805B1

  公开（公告）日：2020-02-05
• 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.