Bicyclic [b]-heteroannelated pyridazine derivatives. Part 6. Aromatization of some tetrahydrotriazolo[4,3-b]pyridazine derivatives with potential activity as benzodiazepine receptor ligands.
Aromatization of the pyridazine ring in 8-aryl-7,8-dihydro-3-trifluoromethyltriazolo[4,3-b]pyridazin -6(5H)-ones in the reaction with a phosphorus pentachloride-phosphorus oxychloride mixture yielded the corresponding 6-chloro compounds. Since halogenation at C-7 was accompanied by an instant 7,8-dehydrohalogenation, the reaction with bromine gave the 7,8-dehydro analogs with no change of the carbonyl function at C-6. Benzoylation yielded the O-benzoyl derivative as found by X-ray crystallography. Substitution of chlorine at C-6 for an amine or thioether function was effected in the reactions with hydrazine, amines, and thiophenols. In vitro tests revealed low affinity of the compounds for the benzodiazepine receptor.
Lange
J
J
Department of Technology and Biotechnology of Drugs, University of Technology, Warsaw, Poland.
Karolak-Wojciechowska
J
J
Gniewosz
M
M
Kuliński
T
T
Plenkiewicz
J
J
D008024:Ligands; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C111457:6-benzyloxy-8-phenyl-3-trifluoromethyltriazolo(4,3-b)pyridazine; D008024:Ligands; D011724:Pyridazines; D011963:Receptors, GABA-A; D014230:Triazoles