(1R,2R)-[2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone | 1119806-44-8

• 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: (1R,2R)-[2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone
• 英文别名: [(1R,2R)-2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone
• CAS: 1119806-44-8
• 化学式: C₁₈H₂₃BrN₂O
• 分子量: 363.297
• InChiKey: QXNSPQZOLIPIJZ-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2R)-[2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone 、 单氧化(~11~C)碳 在 bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)] 、 氨 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成 [carbonyl-¹¹C]AZD5213
  参考文献：
  名称：

  Development of [Carbonyl-¹¹C]AZ13198083, a Novel Histamine Type-3 Receptor Radioligand with Favorable Kinetics

  摘要：

  The histamine subtype-3 receptor (H3R) is implicated in a range of central nervous system disorders, and several radioligands have been developed for H3R positron emission tomography imaging. However, a limitation of currently used PET radioligands for H3R is the slow binding kinetics in high density brain regions. To address this, we herein report the development of three novel candidate H3R radioligands, namely, [carbonyl-C-11]AZ13153556 ([ carbonyl-C-11]4), [carbonyl-C-11]AZD5213([carbonyl-C-11]5), and [carbonyl-C-11]AZ13198083 ([carbonyl-C-11]6), and their subsequent preclinical evaluation in nonhuman primates (NHP). Radioligands [carbonyl-C-11]4-6 were produced and isolated in high radioactivity (>1000 MBq), radiochemical purity (>99%), and moderate molar activity (19-28 GBq/mu mol at time of injection) using a palladium-mediated C-11-aminocarbonylation protocol. All three radioligands showed high brain permeability as well as a regional brain radioactivity distribution in accordance with H3R expression (striatum > cortex > cerebellum). [Carbonyl-C-11]6 displayed the most favorable in vivo kinetics and brain uptake, with an early peak in the striatal time-activity curve followed by a progressive washout from the brain. The specificity and on-target kinetics of [carbonyl-C-11]6 were next investigated in pretreatment and displacement studies. After pretreatment or displacement with 5 (0.1 mg/kg), a uniformly low distribution of radioactivity across the NHP brain was observed. Collectively, this work demonstrates that [carbonyl-C-11]6 is a promising candidate for H3R imaging in human subjects.

  DOI：

  10.1021/acschemneuro.7b00493
• 作为产物：
  描述：

  trans-[2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone 以 甲醇 、 二甲基十二/十四烷基叔胺 、 二氧化碳 为溶剂， 以46%的产率得到(1S,2S)-[2-(4-bromophenyl)cyclopropyl]-(4-cyclobutylpiperazin-1-yl)methanone
  参考文献：
  名称：

  Cyclopropyl Amide Derivatives 978

  摘要：

  本公开至少包括一种环丙基酰胺衍生物，至少包括一种含有本公开的至少一种环丙基酰胺衍生物的药物组合物，以及至少包括一种使用本公开的至少一种环丙基酰胺衍生物用于治疗至少一种与组织胺H3受体相关疾病的方法。

  公开号：

  US20090076020A1

文献信息

• Cyclopropyl Amide Derivatives '978
  申请人：Arnold James

  公开号：US20120065193A1

  公开（公告）日：2012-03-15

  Disclosed herein is at least one cyclopropyl amide derivative, at least one pharmaceutical composition comprising at least one cyclopropyl amide derivative disclosed herein, and at least one method of using at least one cyclopropyl amide derivative disclosed herein for treating at least one histamine H3 receptor associated condition therewith.

  本文披露了至少一种环丙基酰胺衍生物，至少一种包含本文披露的至少一种环丙基酰胺衍生物的药物组合物，以及使用本文披露的至少一种环丙基酰胺衍生物治疗至少一种组织胺H3受体相关疾病的至少一种方法。
• CYCLOPROPYL AMIDE DERIVATIVES
  申请人：ASTRAZENECA AB

  公开号：US20150216861A1

  公开（公告）日：2015-08-06

  Disclosed herein is at least one cyclopropyl amide derivative, at least one pharmaceutical composition comprising at least one cyclopropyl amide derivative disclosed herein, and at least one method of using at least one cyclopropyl amide derivative disclosed herein for treating at least one histamine H3 receptor associated condition therewith.

  本文披露了至少一种环丙基酰胺衍生物，至少一种包含本文披露的至少一种环丙基酰胺衍生物的药物组合物，以及至少一种使用本文披露的至少一种环丙基酰胺衍生物治疗至少一种组织胺H3受体相关疾病的方法。
• Cyclopropyl amide derivatives
  申请人：AstraZeneca AB

  公开号：EP2253615A1

  公开（公告）日：2010-11-24

  Disclosed herein is at least one cyclopropyl amide derivative of formula (I), at least one pharmaceutical composition comprising at least one cyclopropyl amide derivative disclosed herein, and at least one method of using at least one cyclopropyl amide derivative disclosed herein for treating at least one histamine H3 receptor associated condition therewith.

  本文公开了至少一种式（I）的环丙基酰胺衍生物、至少一种包含本文公开的至少一种环丙基酰胺衍生物的药物组合物，以及至少一种使用本文公开的至少一种环丙基酰胺衍生物治疗至少一种组胺 H3 受体相关疾病的方法。
• CYCLOPTOPYL AMIDE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP2195293A2

  公开（公告）日：2010-06-16
• US8063215B2
  申请人：——

  公开号：US8063215B2

  公开（公告）日：2011-11-22