(+/-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one | 1268473-16-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: (+/-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one
• 英文别名: 6-[4-[(2,6-Dichlorophenyl)sulfanylmethyl]phenyl]-6-ethyl-pyrrolo[2,1-d][1,5]benzoxazepin-7-one；6-[4-[(2,6-dichlorophenyl)sulfanylmethyl]phenyl]-6-ethylpyrrolo[2,1-d][1,5]benzoxazepin-7-one
• CAS: 1268473-16-0
• 化学式: C₂₇H₂₁Cl₂NO₂S
• 分子量: 494.441
• InChiKey: IQVNZSWHYXIDAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one 以 乙醇 、 正己烷 、 三乙胺 为溶剂， 生成 (-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one 、 (-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one
  参考文献：
  名称：

  Non-Nucleoside Inhibitors of Human Adenosine Kinase: Synthesis, Molecular Modeling, and Biological Studies

  摘要：

  Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective; and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK. inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.

  DOI：

  10.1021/jm101438u
• 作为产物：
  描述：

  (+/-)-6-ethyl-6-[4-(bromomethyl)phenyl]pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one 、 2,6-二氯苯硫酚 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 14.0h， 以77%的产率得到(+/-)-6-ethyl-6-[4-[(2,6-dichlorophenylthio)methyl]phenyl]6,7-dihydrobenzo[b]pyrrolo[1,2-d][1,4]oxazepin-7-one
  参考文献：
  名称：

  Non-Nucleoside Inhibitors of Human Adenosine Kinase: Synthesis, Molecular Modeling, and Biological Studies

  摘要：

  Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective; and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK. inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.

  DOI：

  10.1021/jm101438u

文献信息

• Non-Nucleoside Inhibitors of Human Adenosine Kinase: Synthesis, Molecular Modeling, and Biological Studies
  作者：Stefania Butini、Sandra Gemma、Margherita Brindisi、Giuseppe Borrelli、Andrea Lossani、Anna Maria Ponte、Andrea Torti、Giovanni Maga、Luciana Marinelli、Valeria La Pietra、Isabella Fiorini、Stefania Lamponi、Giuseppe Campiani、Daniela M. Zisterer、Seema-Maria Nathwani、Stefania Sartini、Concettina La Motta、Federico Da Settimo、Ettore Novellino、Federico Focher

  DOI：10.1021/jm101438u

  日期：2011.3.10

  Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective; and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK. inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells.