N-(2-benzoylphenyl)-2-(2-oxo-4-phenylamino-2H-pyridin-1-yl)acetamide | 1586819-91-1

• 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: N-(2-benzoylphenyl)-2-(2-oxo-4-phenylamino-2H-pyridin-1-yl)acetamide
• 英文别名: 2-(4-anilino-2-oxopyridin-1-yl)-N-(2-benzoylphenyl)acetamide
• CAS: 1586819-91-1
• 化学式: C₂₆H₂₁N₃O₃
• 分子量: 423.471
• InChiKey: BDQFWSFAEGBMON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (4-phenylamino-2-oxo-2H-pyridin-1-yl)-acetic acid 、 2-氨基二苯甲酮 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以53%的产率得到N-(2-benzoylphenyl)-2-(2-oxo-4-phenylamino-2H-pyridin-1-yl)acetamide
  参考文献：
  名称：

  Identification of a new series of amides as non-covalent proteasome inhibitors

  摘要：

  Proteasome inhibition has emerged as an important therapeutic strategy for the treatment of multiple myeloma (MM) and some forms of lymphoma, with potential application in other types of cancers. 20S proteasome consists of three different catalytic activities known as chymotrypsin-like (ChT-L), trypsin-like (T-L), and, post-glutamyl peptide hydrolyzing (PGPH) or caspase-like (C-L), which are located respectively on the beta 5, beta 2, and beta 1 subunits of each heptameric beta rings. Currently a wide number of covalent proteasome inhibitors are reported in literature; however, the less widely investigated non-covalent inhibitors might be a promising alternative to employ in therapy, because of the lack of all drawbacks and side-effects related to irreversible inhibition. In the present work we identified a series of amides, two of which (1b and 1f) are good candidates to non-covalent inhibition of the chymotrypsin-like activity of the 135 proteasome subunit. The non-covalent binding mode was corroborated by docking simulations of the most active inhibitors 1b, 1f and 2h into the yeast 20S proteasome crystal structure. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.022

文献信息

• Identification of a new series of amides as non-covalent proteasome inhibitors
  作者：Kety Scarbaci、Valeria Troiano、Nicola Micale、Roberta Ettari、Lucia Tamborini、Carmen Di Giovanni、Carmen Cerchia、Silvana Grasso、Ettore Novellino、Tanja Schirmeister、Antonio Lavecchia、Maria Zappalà

  DOI：10.1016/j.ejmech.2014.01.022

  日期：2014.4

  Proteasome inhibition has emerged as an important therapeutic strategy for the treatment of multiple myeloma (MM) and some forms of lymphoma, with potential application in other types of cancers. 20S proteasome consists of three different catalytic activities known as chymotrypsin-like (ChT-L), trypsin-like (T-L), and, post-glutamyl peptide hydrolyzing (PGPH) or caspase-like (C-L), which are located respectively on the beta 5, beta 2, and beta 1 subunits of each heptameric beta rings. Currently a wide number of covalent proteasome inhibitors are reported in literature; however, the less widely investigated non-covalent inhibitors might be a promising alternative to employ in therapy, because of the lack of all drawbacks and side-effects related to irreversible inhibition. In the present work we identified a series of amides, two of which (1b and 1f) are good candidates to non-covalent inhibition of the chymotrypsin-like activity of the 135 proteasome subunit. The non-covalent binding mode was corroborated by docking simulations of the most active inhibitors 1b, 1f and 2h into the yeast 20S proteasome crystal structure. (C) 2014 Elsevier Masson SAS. All rights reserved.