benzyl N-[6-(3-chlorophenyl)-2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino]ethyl]pyridin-3-yl]carbamate | 147313-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: benzyl N-[6-(3-chlorophenyl)-2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino]ethyl]pyridin-3-yl]carbamate
• CAS: 147313-44-8
• 化学式: C₂₇H₂₇ClF₃N₃O₅
• 分子量: 565.977
• InChiKey: QKRHCBADVLUYKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 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：

  benzyl N-[6-(3-chlorophenyl)-2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino]ethyl]pyridin-3-yl]carbamate 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 为溶剂， 生成 {6-(3-Chloro-phenyl)-2-oxo-1-[(3,3,3-trifluoro-1-isopropyl-2-oxo-propylcarbamoyl)-methyl]-1,2-dihydro-pyridin-3-yl}-carbamic acid benzyl ester
  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-氯苯乙酮 在 二苯基磷酸 、 四丁基氟化铵 、 氢溴酸 、 sodium methylate 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 溶剂黄146 为溶剂， 生成 benzyl N-[6-(3-chlorophenyl)-2-oxo-1-[2-oxo-2-[(1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino]ethyl]pyridin-3-yl]carbamate
  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

• 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.