1-(3-amino-1H-1,2,4-triazol-5-yl)-N-(4-chlorophenethyl)-N-isobutylpiperidin-4-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(3-amino-1H-1,2,4-triazol-5-yl)-N-(4-chlorophenethyl)-N-isobutylpiperidin-4-amine
• 英文别名: 1-(5-amino-1H-1,2,4-triazol-3-yl)-N-[2-(4-chlorophenyl)ethyl]-N-(2-methylpropyl)piperidin-4-amine
• 化学式: C₁₉H₂₉ClN₆
• 分子量: 376.932
• InChiKey: BADSWYIEDNZIEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  74.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯苯乙胺 在 盐酸 、 三乙酰氧基硼氢化钠 、 potassium carbonate 作用下， 以 乙酸乙酯 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 6.0h， 生成 1-(3-amino-1H-1,2,4-triazol-5-yl)-N-(4-chlorophenethyl)-N-isobutylpiperidin-4-amine
  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

• [EN] SUBSTITUTED AMINO TRIAZOLES, AND METHODS USING SAME<br/>[FR] TRIAZOLES AMINO-SUBSTITUÉS ET PROCÉDÉS D'UTILISATION
  申请人：INST DRUG DELIVERY

  公开号：WO2015095701A1

  公开（公告）日：2015-06-25

  Disclosed are novel substituted amino triazoles of Formula (I), and pharmaceutically acceptable salts thereof. The compounds of Formula (I) are inhibitors of Acidic mammalian chitinase (AMCase) and are useful, in a non-limiting example, for treating asthma. Also provided are pharmaceutical compositions containing at least one compound of the present invention, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and at least one pharmaceutically acceptable carrier, solvent, adjuvant or diluent, and methods of using such compounds and/or compositions to treat asthma and/or to monitor asthma treatment.

  公开了化合物的新型替代氨基三唑的结构，其化学式为（I），以及其药学上可接受的盐。化合物的化学式（I）是酸性哺乳动物几丁质酶（AMCase）的抑制剂，并且在非限制性示例中用于治疗哮喘。还提供了含有本发明至少一种化合物或其药学上可接受的盐、水合物或溶剂化合物的药物组合物，以及至少一种药学上可接受的载体、溶剂、辅料或稀释剂，并使用这些化合物和/或组合物来治疗哮喘和/或监测哮喘治疗的方法。
• SUBSTITUTED AMINO TRIAZOLES, AND METHODS USING SAME
  申请人：The Institute For Drug Delivery

  公开号：EP3082805A1

  公开（公告）日：2016-10-26
• 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.