Synthesis, central and peripheral benzodiazepine receptor affinity of pyrazole and pyrazole-containing polycyclic derivatives.
A series of new pyrazole-condensed 6,5,5 tricyclic compounds were synthesized and tested to evaluate their binding affinities at both central (CBR) and peripheral (PBR) benzodiazepine receptors. Some 1-aryl-5-phenylpyrazole derivatives were also prepared and tested for comparison with their corresponding rigid tricyclic analogs. Among the newly synthesized 1-aryl-1,4-dihydro-indeno[1,2-c]pyrazoles bearing both an ethoxycarbonyl group at position 3 and a carbonyl function at the position 4, compound 4b emerged as a new potent (IC(50) = 26.4 nM) and selective CBR ligand. The 4-oxo-1-aryl-1,4-dihydro-indeno[1,2-c]pyrazole diethylamide derivative 14a was instead identified as a relatively potent (IC(50) = 124 nM) but highly selective PBR ligand.
Campagna
Francesco
F
Dipartimento Farmacochimico, Università di Bari, via Orabona 4, 70126 Bari, Italy. Campagna@farmchim.uniba.it
Palluotto
Fausta
F
Carotti
Angelo
A
Maciocco
Elisabetta
E
D000818:Animals; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
D008024:Ligands; D011084:Polycyclic Aromatic Hydrocarbons; D011720:Pyrazoles; D011963:Receptors, GABA-A