2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide | 147269-64-5

• 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: 2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide
• 英文别名: benzyl N-[6-methyl-2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino]ethyl]pyridin-3-yl]carbamate
• CAS: 147269-64-5
• 化学式: C₂₂H₂₆F₃N₃O₅
• 分子量: 469.461
• InChiKey: ANLVDJJXKKLCGI-UHFFFAOYSA-N

物化性质

• 沸点：
  666.5±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide 在 二氯乙酸 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 生成 2-(3-Benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-aryl-2-oxopyridyl Trifluoromethyl Ketones

  摘要：

  A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.

  DOI：

  10.1021/jm00046a015
• 作为产物：
  描述：

  3-氰基-6-甲基-2(1H)-吡啶酮 在 N-甲基吗啉 、 二苯基磷酸 、 氢溴酸 、 sodium hydride 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1-羟基苯并三唑一水物 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 溶剂黄146 为溶剂， 生成 2-(3-benzyloxycarbonylamino-6-methyl-2-oxo-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl)acetamide
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-aryl-2-oxopyridyl Trifluoromethyl Ketones

  摘要：

  A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.

  DOI：

  10.1021/jm00046a015

文献信息

• Heterocyclic amides having HLE inhibiting activity
  申请人：ZENECA LIMITED

  公开号：EP0509769A2

  公开（公告）日：1992-10-21

  The present invention relates to certain novel heterocyclic amides which are 1-pyridylacetamide compounds of formula I, set out herein, which are inhibitors of human leukocyte elastase (HLE), also known as human neutrophil elastase (HNE), making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated. The invention also includes intermediates useful in the synthesis of these heterocyclic amides, processes for preparing the heterocyclic amides, pharmaceutical compositions containing such heterocyclic amides and methods for their use.

  本发明涉及某些新型杂环酰胺，它们是式I的1-吡啶基乙酰胺化合物，载于本发明中，它们是人白细胞弹性蛋白酶（HLE），也称为人中性粒细胞弹性蛋白酶（HNE）的抑制剂，使得它们在任何需要这种抑制的情况下都有用，例如在药理学、诊断学和相关研究中用作研究工具，以及在治疗哺乳动物中涉及HLE的疾病时。本发明还包括用于合成这些杂环酰胺的中间体、制备杂环酰胺的工艺、含有这些杂环酰胺的药物组合物及其使用方法。
• US5521179A
  申请人：——

  公开号：US5521179A

  公开（公告）日：1996-05-28
• Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-aryl-2-oxopyridyl Trifluoromethyl Ketones
  作者：James R. Damewood、Philip D. Edwards、Scott Feeney、Bruce C. Gomes、Gary B. Steelman、Paul A. Tuthill、Joseph C. Williams、Peter Warner、Sheila A. Woolson

  DOI：10.1021/jm00046a015

  日期：1994.9

  A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.