title: The cyano-NNO-azoxy function in the design of an irreversible label for alpha 1 adrenoreceptors.
abstract: A potential alpha 1-adrenergic irreversible antagonist 6, containing the cyano-NNO-azoxy function was synthesized and tested. The effects of norepinephrine on rat thoracic aorta were irreversibly blocked by this compound at the concentration of 1 x 10(-5) M after 60 minutes. Binding studies showed that 6, at 1 x 10(-6) M, did not modify the KD of Prazosin and caused a 30% decrease of the Bmax. Substitution in 6 of the bis (2-chloroethyl)amino moiety for the cyano-NNO-azoxy function afforded 7 which behaves as an irreversible antagonist able to change KD of Prazosin without influencing Bmax.
authors.affiliation: Dipartimento di Scienza e Technologia del Farmaco, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sorba
authors.forename: A
authors.initials: A
authors.lastname: Di Stilo
authors.forename: C
authors.initials: C
authors.lastname: Medana
authors.forename: C
authors.initials: C
authors.lastname: Cena
authors.forename: A
authors.initials: A
authors.lastname: Gasco
authors.forename: M
authors.initials: M
authors.lastname: Orsetti
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: C094389:1-(4-amino-6,7--dimethoxy-2-quinazolyl)-4-benzoylpiperazine; C094388:1-(4-amino-6,7-dimethoxy-2--quinazolyl)-4-(4-(bis-2-chloroethylamino)benzoyl)piperazine; C094387:1-(4-amino-6,7-dimethoxy-2-quinazolyl)-4-(4-(cyano-NNO-azoxy)benzoyl)piperazine; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine; D011224:Prazosin