Benzodiazepine receptor ligands. III. Synthesis and biological evaluation of 2- and/or 3-substituted pyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides.
A new series of 2- and/or 3-substituted pyrazolo [5,1-c][benzotriazine 5-oxides and their 8-chloro derivatives were synthesized, and their benzodiazepine receptor (BZR) affinities were evaluated in vitro in comparison to lead compound 3-ethoxycarbonyl-8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (29) [1,2]. None of the new compounds showed significant affinity for BZR. On the basis of a pharmacophore/receptor model suggested for lead compound 29, some hypotheses to explain the inactivity of new derivatives are discussed.
Guerrini
G
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Firenze, Florence, Italy.
Costanzo
A
A
Bruni
F
F
Ciciani
G
G
Selleri
S
S
Gratteri
P
P
Costa
B
B
Martini
C
C
Lucacchini
A
A
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D005442:Flumazenil / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005445:Flunitrazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018757:GABA Modulators / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011963:Receptors, GABA-A / Q000187:drug effects*; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D018757:GABA Modulators; D011720:Pyrazoles; D011963:Receptors, GABA-A; D014227:Triazines; D005442:Flumazenil; D005445:Flunitrazepam