Synthesis and Benzodiazepine Receptor Affinity of Derivatives of the New Tricyclic Heteroaromatic System Pyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyridazin‐3(2H,5H)‐one
Abstract:Derivatives 7-13 of a new tricyclic heteroaromatic system, pyrido[3',2':5,6]thiopyrano[4,3-c]pyridazin-3(2H,5H)-one, were prepared as potential ligands at the benzodiazepine receptor, in view of their structural analogy with potent ligands such as the pyrazoloquinolines of the CGS series II, and especially with the benzothiopyrano[4,3-c]pyridazinones VI. They were obtained starting from the versatile ketones 2,3-dihydrothiopyrano[2,3-b]pyridin-4(4H)-one 1 and the corresponding 7-methyl derivative 2, via conden… Show more
Pyrido[3',2':5,6]thiopyrano[4,3-c]pyridazin-3(2H,5H)-one. -The new tricyclic systems (VII) and (VIII) are obtained via condensation of thiopyranopyridinones (I) with glyoxylic acid (II) and reaction of the intermediate acid mixtures (III), (IV) and (V) with hydrazine or substituted phenylhydrazines (VI). The benzodiazepine receptor ligands display an affinity in the micromolar/submicromolar order, but they show a lower potency than the structurally related ligands in the benzothiopyranopyridazinone series. -(PRIMOFIORE*, G.; DA SETTIMO, F.; MARINI, A. M.; SIMORINI, F.; LA MOTTA, C.; TALIANI, S.; LANERI, S.; TRINCAVELLI, L.; MARTINI, C.; Arch. Pharm. (Weinheim, Ger.) 338 (2005) 2-3, 126-132; Dip. Sci. Farm., Univ. Pisa, I-56126 Pisa, Italy; Eng.) -H. Hoennerscheid 34-207
Pyrido[3',2':5,6]thiopyrano[4,3-c]pyridazin-3(2H,5H)-one. -The new tricyclic systems (VII) and (VIII) are obtained via condensation of thiopyranopyridinones (I) with glyoxylic acid (II) and reaction of the intermediate acid mixtures (III), (IV) and (V) with hydrazine or substituted phenylhydrazines (VI). The benzodiazepine receptor ligands display an affinity in the micromolar/submicromolar order, but they show a lower potency than the structurally related ligands in the benzothiopyranopyridazinone series. -(PRIMOFIORE*, G.; DA SETTIMO, F.; MARINI, A. M.; SIMORINI, F.; LA MOTTA, C.; TALIANI, S.; LANERI, S.; TRINCAVELLI, L.; MARTINI, C.; Arch. Pharm. (Weinheim, Ger.) 338 (2005) 2-3, 126-132; Dip. Sci. Farm., Univ. Pisa, I-56126 Pisa, Italy; Eng.) -H. Hoennerscheid 34-207
Regioisomeric [c]annulated pyridazines were prepared from arylhydrazines and carbocyclic or heterocyclic β‐oxo esters with an α‐phenacetyl moiety. With AcOH/EtOH, the hydrazones were preferentially formed at the endocyclic ketone, which are further cyclized with trifluoroacetic acid (TFA)/CH2Cl2 to give 2,4a‐dihydropyridazines. Use of TFA/CH2Cl2 led hydrazones at the exocyclic benzoyl group, which reacted further to give 1,4‐dihydro‐4aH‐pyridazines. In this investigation, examples of the rare or unknown heterocyclic systems furo[3,4‐c]‐, thiopyrano[4,3‐c]‐ and pyrido[4,3‐c]pyridazine were prepared.
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