Synthesis and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[11C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one, a potential PET tracer for growth hormone secretagogue receptor (GHSR).
Synthesis and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[11C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one, a potential PET tracer for growth hormone secretagogue receptor (GHSR).
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(S)-6-(4-氟苯氧基)-3-((1-[11C]甲基哌啶-3-基)甲基)-2-邻甲苯基喹唑啉-4(3H)-酮的合成和体内评价
DOI：
10.1016/j.bmc.2011.02.021
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发表时间：
2011
影响因子：
3.5
通讯作者：
Wahl,RichardL
中科院分区：
文献类型：
--
作者：
Potter,Rachel;Horti,AndrewG;Ravert,HaydenT;Holt,DanielP;Finley,Paige;Scheffel,Ursula;Dannals,RobertF;Wahl,RichardL
多肽激素Ghrelin通过作用于其受体生长激素促分泌素受体(GHSR)，在多种代谢功能中发挥重要作用，包括刺激食欲、体重增加和抑制胰岛素分泌。鉴于肥胖是困扰现代社会的主要健康问题之一，Ghrelin信号系统仍然是治疗肥胖症的重要和有吸引力的药理靶点。GHSR的体内成像可以揭示Ghrelin影响摄食行为的机制，从而为开发有效的治疗方法提供新的治疗视角。近年来，一系列哌啶取代的喹唑烷酮类化合物被报道为具有高结合亲和力的选择性强的GHSR拮抗剂。本文描述了(S)-6-(4-fluorophenoxy)-3-((1-[11C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one([11C]1)的合成、体外和体内评价，[11C]1是一种潜在的用于成像GHSR的PET放射性配体。
The peptide hormone ghrelin mediates through action on its receptor, the growth hormone secretagogue receptor (GHSR), and is known to play an important role in a variety of metabolic functions including appetite stimulation, weight gain, and suppression of insulin secretion. In light of the fact that obesity is one of the major health problems plaguing the modern society, the ghrelin signaling system continues to remain an important and attractive pharmacological target for the treatment of obesity. In vivo imaging of the GHSR could shed light on the mechanism by which ghrelin affects feeding behavior and thus offers a new therapeutic perspective for the development of effective treatments. Recently, a series of piperidine-substituted quinazolinone derivatives was reported to be selective and potent GHSR antagonists with high binding affinities. Described herein is the synthesis, in vitro, and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[11C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one ([11C]1), a potential PET radioligand for imaging GHSR.