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.
Selleri
Silvia
S
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff, 6, 50019 Sesto F.no Firenze, Italy.
Gratteri
Paola
P
Costagli
Camilla
C
Bonaccini
Claudia
C
Costanzo
Annarella
A
Melani
Fabrizio
F
Guerrini
Gabriella
G
Ciciani
Giovanna
G
Costa
Barbara
B
Spinetti
Francesca
F
Martini
Claudia
C
Bruni
Fabrizio
F
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