Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as peripheral benzodiazepine receptor ligands: synthesis, biological evaluation and 3D-QSAR investigation.
The present paper reports the synthesis and binding studies of new 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as selective Peripheral Benzodiazepine Receptor (PBR) ligands. The variability of substituents at the 3-position was investigated and a 3D-QSAR model was proposed to evaluate the effect of different substitutions on the acetamide moiety. In addition, a subset of the novel compounds showing high affinity for PBR was tested for their ability to modulate the steroid biosynthesis in C6 glioma cells.
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff, 6, 50019 Sesto F.no Firenze, Italy.
Silvia
S
Selleri
Paola
P
Gratteri
Camilla
C
Costagli
Claudia
C
Bonaccini
Annarella
A
Costanzo
Fabrizio
F
Melani
Gabriella
G
Guerrini
Giovanna
G
Ciciani
Barbara
B
Costa
Francesca
F
Spinetti
Claudia
C
Martini
Fabrizio
F
Bruni
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D058787:GABA-A Receptor Antagonists; D005910:Glioma / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015335:Molecular Probes; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis
D000081:Acetamides; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D015335:Molecular Probes; D011743:Pyrimidines; D011963:Receptors, GABA-A; D013256:Steroids