title: Synthesis of fluorine substituted pyrazolopyrimidines as potential leads for the development of PET-imaging agents for the GABAA receptors.
abstract: 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.
authors.affiliation: ABX advanced biochemical compounds GmbH, H.-Gläser-Str. 10-14, D-01454 Radeberg, Germany. hoepping@abx.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoepping
authors.forename: Michael
authors.initials: M
authors.lastname: Diekers
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheunemann
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Achim
authors.initials: A
authors.lastname: Hiller
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D005260:Female; D005461:Fluorine / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; D005461:Fluorine; C031280:pyrazole; C030986:pyrimidine