(6-Benzyl-3-benzyloxycarbonylamino-2-oxo-2H-pyridin-1-yl)-acetic acid tert-butyl ester | 1026825-74-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (6-Benzyl-3-benzyloxycarbonylamino-2-oxo-2H-pyridin-1-yl)-acetic acid tert-butyl ester
• 英文别名: Tert-butyl 2-[6-benzyl-2-oxo-3-(phenylmethoxycarbonylamino)pyridin-1-yl]acetate
• CAS: 1026825-74-0
• 化学式: C₂₆H₂₈N₂O₅
• 分子量: 448.519
• InChiKey: TVDPGCJEJSJTNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6-Benzyl-3-benzyloxycarbonylamino-2-oxo-2H-pyridin-1-yl)-acetic acid tert-butyl ester 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 生成 {6-Benzyl-3-[(naphthalene-1-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-acetic acid
  参考文献：
  名称：

  PYRIDONE-BASED PEPTIDOMIMETIC INHIBITORS OF INTERLEUKIN-1β-CONVERTING ENZYME (ICE)

  摘要：

  New potent, reversible inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P-2-P-3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00220-5
• 作为产物：
  描述：

  苯基丙酮 在 二苯基磷酸 、 氢溴酸 、 sodium methylate 、 哌啶乙酸盐 、 sodium hydride 、 三乙胺 作用下， 以 1,4-二氧六环 、 溶剂黄146 为溶剂， 生成 (6-Benzyl-3-benzyloxycarbonylamino-2-oxo-2H-pyridin-1-yl)-acetic acid tert-butyl 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

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.
• PYRIDONE-BASED PEPTIDOMIMETIC INHIBITORS OF INTERLEUKIN-1β-CONVERTING ENZYME (ICE)
  作者：Graeme Semple、Doreen M Ashworth、Graham R Baker、Andrzej R Batt、Andrew J Baxter、David W.M Benzies、Lucy H Elliot、D.Michael Evans、Richard J Franklin、Peter Hudson、Paul D Jenkins、Gary R Pitt、David P Rooker、Andrew Sheppard、Michael Szelke、Satoshi Yamamoto、Yasuo Isomura

  DOI：10.1016/s0960-894x(97)00220-5

  日期：1997.5

  New potent, reversible inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P-2-P-3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents. (C) 1997 Elsevier Science Ltd.