(7BR,10AR)-2,3,4,7B,8,9,10,10A-八氢-1H-环戊并[B][1,4]二氮杂革O[6,7,1-HI]吲哚盐酸盐 | 428868-35-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: (7BR,10AR)-2,3,4,7B,8,9,10,10A-八氢-1H-环戊并[B][1,4]二氮杂革O[6,7,1-HI]吲哚盐酸盐
• 英文名称: (7bR,10aR)-2,3,4,7b,8,9,10,10a-octahydro-1H-cyclopenta[b][1,4]diazepino[6,7,1-hi]indole hydrochloride
• 英文别名: (11R,15R)-7,10-diazatetracyclo[8.5.1.05,16.011,15]hexadeca-1,3,5(16)-triene;hydrochloride
• CAS: 428868-35-3
• 化学式: C₁₄H₁₈N₂*ClH
• 分子量: 250.771
• InChiKey: UJVFYZZBCUXMDV-LOCPCMAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  15.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,2,3,3a,4,8b-六氢环戊二烯并[b]吲哚 在 硫酸 、 对甲苯磺酸 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 (7BR,10AR)-2,3,4,7B,8,9,10,10A-八氢-1H-环戊并[B][1,4]二氮杂革O[6,7,1-HI]吲哚盐酸盐
  参考文献：
  名称：

  Imaging Evaluation of 5HT_2C Agonists, [¹¹C]WAY-163909 and [¹¹C]Vabicaserin, Formed by Pictet–Spengler Cyclization

  摘要：

  The serotonin subtype 2C (5HT(2C)) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT(2C) full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet-Spengler cyclization with [C-11]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT(2C) agonists. Both radiolabeled molecules exhibit high blood-brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet-Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers.

  DOI：

  10.1021/jm401802f

文献信息

• Imaging Evaluation of 5HT_2C Agonists, [¹¹C]WAY-163909 and [¹¹C]Vabicaserin, Formed by Pictet–Spengler Cyclization
  作者：Ramesh Neelamegam、Tim Hellenbrand、Frederick A. Schroeder、Changning Wang、Jacob M. Hooker

  DOI：10.1021/jm401802f

  日期：2014.2.27

  The serotonin subtype 2C (5HT(2C)) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT(2C) full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet-Spengler cyclization with [C-11]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT(2C) agonists. Both radiolabeled molecules exhibit high blood-brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet-Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers.