isobutyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: isobutyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate
• 英文别名: 2-Methylpropyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate
• 化学式: C₂₄H₂₇ClN₂O₂
• 分子量: 410.944
• InChiKey: AMBATUWSQRROKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  地氯雷他定 、 氯甲酸异丁酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 isobutyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate
  参考文献：
  名称：

  Loratadine and Analogues: Discovery and Preliminary Structure–Activity Relationship of Inhibitors of the Amino Acid Transporter B⁰AT2

  摘要：

  B(0)AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B(0)AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family. Reversible inhibition of B(0)AT2 was confirmed by electrophysiology. A series of loratadine analogues were synthesized to gain insight into the structure-activity relationships. Our studies provide the first chemical tool for B(0)AT2.

  DOI：

  10.1021/jm501086v

文献信息

• Loratadine and Analogues: Discovery and Preliminary Structure–Activity Relationship of Inhibitors of the Amino Acid Transporter B⁰AT2
  作者：Serena Cuboni、Christian Devigny、Bastiaan Hoogeland、Andrea Strasser、Sebastian Pomplun、Barbara Hauger、Georg Höfner、Klaus T. Wanner、Matthias Eder、Armin Buschauer、Florian Holsboer、Felix Hausch

  DOI：10.1021/jm501086v

  日期：2014.11.26

  B(0)AT2, encoded by the SLC6A15 gene, is a transporter for neutral amino acids that has recently been implicated in mood and metabolic disorders. It is predominantly expressed in the brain, but little is otherwise known about its function. To identify inhibitors for this transporter, we screened a library of 3133 different bioactive compounds. Loratadine, a clinically used histamine H1 receptor antagonist, was identified as a selective inhibitor of B(0)AT2 with an IC50 of 4 μM while being less active or inactive against several other members of the SLC6 family. Reversible inhibition of B(0)AT2 was confirmed by electrophysiology. A series of loratadine analogues were synthesized to gain insight into the structure-activity relationships. Our studies provide the first chemical tool for B(0)AT2.