Synthesis, benzodiazepine receptor binding and molecular modelling of isochromeno[4,3-c]pyrazol-5(1H)-one derivatives.
A series of isochromeno[4,3-c]pyrazole-5(1H)-one derivatives 7b-h were prepared and tested at 10 μM for their ability to displace specific [(3)H]flunitrazepam from bovine brain membranes. The substitution pattern of the above derivatives was shown to influence the receptor affinity. The most active compound of the series was 7e, showing a 54% inhibition of [(3)H]flunitrazepam binding. Compounds 7a-d,i were compared with the known isomers chromeno[4,3-c]pyrazole-4(1H)-ones 14a-d,i, showing that the isochromene/chromene isomerism influences the activity.
Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari-Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy. benedetta.maggio@unipa.it
B
B
Maggio
D
D
Raffa
M V
MV
Raimondi
F
F
Plescia
M L
ML
Trincavelli
C
C
Martini
F
F
Meneghetti
L
L
Basile
S
S
Guccione
G
G
Daidone
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*
D001578:Benzopyrans; D011720:Pyrazoles; D011963:Receptors, GABA-A