Titre du document / Document title

Synthesis and α₁-antagonist activity of new prazosin- and benextramine-related tetraamine disulfides

Auteur(s) / Author(s)

GIARDINA D. ⁽¹⁾ ; CRUCIANELLI M. ⁽¹⁾ ; GULINI U. ⁽¹⁾ ; MARUCCI G. ⁽¹⁾ ; MELCHIORRE C. ⁽²⁾ ; SPAMPINATO S. ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Chemical Sciences, University of Camerino, Via S Agostino 1, 62032 Camerino, ITALIE
⁽²⁾ Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, ITALIE
⁽³⁾ Department of Pharmacology, University of Bologna, Via Irnerio 48, 40126 Bologna, ITALIE

Résumé / Abstract

Tetraamine disulfides 1-10 were designed by combining the structural features of benextramine, an irreversible α₁/α₂-adrenoceptor antagonist, and prazosin, a selective competitive α₁-antagonist. Their biological profile was assessed by functional and binding assays. In rat vas deferens functional experiments, tetraamine disulfides 1-10 displayed a marked selectivity at α₁-adrenoceptors. Furthermore, they acted as competitive antagonists at α₁-adrenoceptors and weak noncompetitive (irreversible) antagonists at α₂-adrenoceptors. In binding assays, performed at α₁-adrenoceptors of rat liver (α_1B) and submaxillary gland (α_1A), compound 5 showed an 11-fold selectivity for α_1B-adrenoceptors in contrast to both prazosin and benextramine, which were not selective or selective for the α_1A-subtype respectively.

Revue / Journal Title

European journal of medicinal chemistry   ISSN 0223-5234   CODEN EJMCA5 

Source / Source

1997, vol. 32, n^o1, pp. 9-20 (50 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Oxford, ROYAUME-UNI  (1974) (Revue)

Mots-clés anglais / English Keywords

Structure activity relation ; Chemical synthesis ; Quinazoline derivatives ; Aminosulfide ; Aliphatic compound ; Prazosin ; Antagonist ; α1-Adrenergic receptor ; Affinity ; In vitro ; Rat ; Animal ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Relation structure activité ; Synthèse chimique ; Quinazoline dérivé ; Aminosulfure ; Composé aliphatique ; Prazosine ; Antagoniste ; Récepteur α1-adrénergique ; Affinité ; In vitro ; Rat ; Animal ; Récepteur α1B-adrénergique ; Récepteur α1A-adrénergique ; Bénextramine ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Relación estructura actividad ; Síntesis química ; Aminosulfuro ; Compuesto alifático ; Prazosina ; Antagonista ; Receptor α1-adrenérgico ; Afinidad ; In vitro ; Rata ; Animal ; Rodentia ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 12640, 35400006227418.0020