Synthesis and anxiolytic activity of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines

Abstract

The synthesis of a series of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines (VIII) is reported. Some of these derivatives show activity in tests predictive of anxiolytic activity [(a) protection against pentylenetetrazole-induced convulsions; (b) thirsty rat conflict procedure]. They also represent a new class of compound which inhibits [3H]diazepam binding. Structure--activity correlations, as well as the ability of structures VIII to inhibit [3H]diazepam binding (in vitro), are discussed.

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.…”

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

“…The chemical structure of SR95195 differs from that of CL218,872 not only in the position of the phenyl ring, but also in the absence of a CF3 substituent on the phenyl. However, in the 6-phenyl-triazolopyridazine series the compound which is not substituted on the phenyl ring has been shown to have the same pharmacological profile as CL 218,872, but to be slightly less potent (Albright et al, 1981 (Cowen et al, 1981;Oakley & Jones, 1982;Braestrup et al, 1982;File, 1983) whereas the BZD receptor antagonist, Ro 15-1788 does not lower seizure threshold . Thus the induc-tion of seizures by SR 95195 strongly suggests this compound is an inverse BZD agonist.…”

Synthesis of (2,2,2-trifluoroethyl) substituted pyridazin-3(2H)-ones and 1,5-dihydropyrrol-2-ones from α,β-unsaturated γ-lactones and hydrazines

“…Pyridazin-3(2H)-ones have generally been prepared from gketo derivatives (acid or corresponding chloride, ester) [5], and various substituted hydrazines via dihydro intermediates, using multi-step sequence. g-Lactones (saturated or a, b-unsaturated) have also been used as starting materials [6,7].…”