Details

Autor(en) / Beteiligte

• HOEPPING, Alexander
• DIEKERS, Michael
• DEUTHER-CONRAD, Winnie
• SCHEUNEMANN, Matthias
• FISCHER, Steffen
• HILLER, Achim
• WEGNER, Florian
• STEINBACH, Jörg
• BRUST, Peter

Titel

Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors

Ist Teil von

• Bioorganic & medicinal chemistry, 2008-02, Vol.16 (3), p.1184-1194

Ort / Verlag

Oxford: Elsevier Science

Erscheinungsjahr

2008

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Neuroimaging of GABA(A) receptors offers the potential for a better diagnosis of 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 (5b) showed an IC(50) value of 2.78+/-0.63 nM comparable to the lead compound Indiplon (IC(50) 3.29+/-0.37 nM), thus making it an interesting candidate for further investigations. In addition to the fluorinated reference compounds, suitable precursors for (18)F-radiolabelling studies have been synthesized.