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Synthesis and Benzodiazepine Receptor Affinity of Derivatives of the New Tricyclic Heteroaromatic System Pyrido[3′,2′:5,6]thiopyrano[4,3‐ c ]pyridazin‐3(2 H ,5 H )‐one
Author(s) -
Primofiore Giampaolo,
Da Settimo Federico,
Marini Anna Maria,
Simorini Francesca,
La Motta Concettina,
Taliani Sabrina,
Laneri Sonia,
Trincavelli Letizia,
Martini Claudia
Publication year - 2005
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200400948
Subject(s) - diazepine , chemistry , tricyclic , glyoxylic acid , stereochemistry , hydrazine (antidepressant) , derivative (finance) , benzodiazepine , bicyclic molecule , receptor , ring (chemistry) , organic chemistry , biochemistry , financial economics , economics
Derivatives 7 – 13 of a new tricyclic heteroaromatic system, pyrido[3′,2′:5,6]thiopyrano[4,3‐ c ]pyridazin‐3(2 H ,5 H )‐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(4 H )‐one 1 and the corresponding 7‐methyl derivative 2 , via condensation with glyoxylic acid, and reaction of the intermediate acid mixtures with hydrazine or substituted phenylhydrazines. When evaluated for their binding affinity at the benzo diazepine receptor in bovine cortical membranes, the target compounds 8 – 13 displayed an affinity in the micromolar/submicromolar order. A hypothesis is presented to rationalize these results.