Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine derivatives. 3. New 6-(3-thienyl) series as alpha 1 selective ligands.
New 3-aryl-6-(3-thienyl)pyrazolo[1,5-a]pyrimidin-7-ones (2a-j) are synthesized and evaluated in vitro on Bz/GABA(A) receptors and on recombinant benzodiazepine receptors (alpha x beta 2/3 gamma 2; x = 1-3, 5) expressed in HEK293 cells. SAR studies on the new compounds are conducted and molecular modeling is accomplished to better investigate requirements leading to subtype selectivity. Some of the synthesized compounds are tested in vivo to explore their pharmacological effect as a consequence of their high alpha 1 beta 2 gamma 2 subtype selectivity observed in vitro.
Selleri
Silvia
S
Department of Pharmaceutical Sciences, University of Firenze, Via G. Capponi 9, 50121 Firenze, Italy. silvia.selleri@unifi.it
Bruni
Fabrizio
F
Costagli
Camilla
C
Costanzo
Annarella
A
Guerrini
Gabriella
G
Ciciani
Giovanna
G
Gratteri
Paola
P
Bonaccini
Claudia
C
Malmberg Aiello
Petra
P
Besnard
François
F
Renard
Stephane
S
Costa
Barbara
B
Martini
Claudia
C
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D008024:Ligands; D009125:Muscle Relaxants, Central; D011743:Pyrimidines; D011963:Receptors, GABA-A