(+/-)-6-(p-tolyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-(6H)-one | 1268473-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (+/-)-6-(p-tolyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-(6H)-one
• 英文别名: 6-(4-Methylphenyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-one
• CAS: 1268473-58-0
• 化学式: C₁₉H₁₅NOS
• 分子量: 305.4
• InChiKey: MLVYZUTYSALVMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-6-(p-tolyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-(6H)-one 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium hydride 作用下， 以 四氢呋喃 、 四氯化碳 、 mineral oil 为溶剂， 反应 19.5h， 生成 (+/-)-6-ethyl-6-(4-bromomethylphenyl)pyrrolo[2,1-d][1,5]-benzothiazepin-7(6H)-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：

  双(2-N-吡咯基苯基)二硫化物 在 sodium tetrahydroborate 、 五氯化磷 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 27.5h， 生成 (+/-)-6-(p-tolyl)pyrrolo[2,1-d][1,5]benzothiazepin-7-(6H)-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