A 7‐phenyl substituted triazolopyridazine has inverse agonist activity at the benzodiazepine receptor site

Abstract

1 To investigate further the structural requirements for benzodiazepine (BZD) receptor ligands, we synthesized SR.95195, [7-phenyl-3-methyl-1,2,4-triazolo-(4,3-b) pyridazine], a positional isomer of the 6-phenyl-triazolo-pyridazines, which were the first non-BZD derivatives to exhibit high affinity for the BZD receptor and BZD-like activity in vivo. (EDm: 8.6 mg kg-', i.p.), but not that of pentobarbitone 15 mg kg-', i.p.5 It is concluded that SR 95195 has the pharmacological profile of an inverse BZD agonist and that displacing the phenyl from the 6-to the 7-position in the triazolopyridazine series causes a shift from agonist to inverse agonist type activity at the BZD receptor site.

Synthesis and in vitro cytotoxicity studies of novel triazolo[4,3-b]pyridazinones

“…The reaction of compounds 2e-f with N-aryl-Cethoxycarbonylnitrile imines, generated in situ from ethylhydrazono--bromoglyoxylates 1a-d [15] and triethylamine, was performed in tetrahydrofuran (THF) at room temperature. In all cases, only one type of triazolopyridazinone (3)(4)(5)(6)(7)(8)(9) was obtained in moderate to good yields (Scheme 1). No adduct resulting from a condensation on the double bond C=O was detected under identical conditions.…”

“…Triazolopyridazine derivatives are frequently used in biological research as adenine receptor ligands [7][8][9]. In our ongoing research program aiming at new pyridazino-fused ring systems [10], we report herein the synthesis of the triazolo[4,3-b]pyridazinones 3-9, which were obtained by 1,3-dipolar cycloaddition.…”

Facile Synthesis of New [1,2,4]Triazolo[4,3‐b]pyridazine

“…In the last decades, the chemistry of triazolo[4,3‐ b ]pyridazine derivatives has received considerable attention owing to their varied biological activities, such as antiviral , antitumor , sedative/hypnotic , anti‐anxiety , adenine receptor ligand , hypotensive, herbicidal, pesticidal , bactericidal and anti‐HAV activity . In the light of these information and due to our continuing interest in the synthesis of biologically important heterocycles in this paper, we wish to report the facile syntheses of some new derivatives of triazolo[4,3‐ b ]pyridazines.…”

Anti‐HAV Activity of Some Newly Synthesized Triazolo[4,3‐b]pyridazines

“…In the last few decades, the chemistry of triazolo [4,3-b]pyridazine derivatives has received considerable attention owing to their variety of biological activities, especially as a potential antiviral [1], antitumoral [2,3], sedative/hypnotic [4], anti-anxiety [5 -7], adenine receptor ligand [8,9], hypotensive and heart rate activity [10], as herbicidal, pesticidal [11], and bactericidal [12]. In connection with our research program for the synthesis of different fused heterocyclic compounds with antiviral [1,13,14] and antimicrobial interest [15 -19], we describe the syntheses of some triazolo [4,3-b]pyridazine derivatives with promising anti-HAV activity.…”