Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors
作者:Alexander Hoepping、Michael Diekers、Winnie Deuther-Conrad、Matthias Scheunemann、Steffen Fischer、Achim Hiller、Florian Wegner、Jörg Steinbach、Peter Brust
DOI:10.1016/j.bmc.2007.10.079
日期:2008.2.1
diseases related to a dysfunction of the GABAergic neurotransmission. A series of potent fluorinated analogues of the pyrazolopyrimidine Indiplon has been synthesized and evaluated in vitro as potential agents for imaging the GABA(A) receptor by means of positron emission tomography (PET). The most promising compound N-(3-fluoropropyl)-N-[3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]- phenyl]-acetamide
GABA(A)受体的神经影像学为更好地诊断与GABA能神经传递功能障碍有关的疾病提供了潜力。合成了一系列吡唑并嘧啶Indiplon的有效氟化类似物,并进行了体外评估,作为通过正电子发射断层扫描(PET)成像GABA(A)受体的潜在药物。最有前途的化合物N-(3-氟丙基)-N- [3- [3-(噻吩-2-羰基)-吡唑并[1,5-a]嘧啶-7-基]-苯基]-乙酰胺(5b)与铅化合物Indiplon(IC(50)3.29 +/- 0.37 nM)可比的IC(50)值为2.78 +/- 0.63 nM,因此使其成为进一步研究的有趣候选者。除氟化参考化合物外,还合成了适用于(18)F-放射性标记研究的前体。