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Alpha1-adrenoceptor antagonists. 6. Structural optimization of pyridazinone-arylpiperazines. Study of the influence on affinity and selectivity of cyclic substituents at the pyridazinone ring and alkoxy groups at the arylpiperazine moiety.
Betti, Laura; Corelli, Federico; Floridi, Monia; Giannaccini, Gino; Maccari, Laura; Manetti, Fabrizio; Strappaghetti, Giovannella; Botta, Maurizio.
Afiliación
  • Betti L; Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
J Med Chem ; 46(16): 3555-8, 2003 Jul 31.
Article en En | MEDLINE | ID: mdl-12877594
In continuing our search for selective alpha(1)-adrenoceptor (AR) antagonists, we have synthesized new alkoxyarylpiperazinylalkylpyridazinone derivatives. The new compounds were tested for their affinity toward alpha(1)- and alpha(2)-AR and toward the 5-HT(1A) receptor. alpha(1)-AR affinity data are in the subnanomolar range, with 3 showing an affinity of 0.052 nM, about 5-fold higher than prazosin. None of the studied compounds was found to be alpha(1)/alpha(2) selective, but 8 showed an interesting 5-HT(1A)/alpha(1) affinity ratio of 119.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperazinas / Piridazinas / Receptores Adrenérgicos alfa 1 / Antagonistas Adrenérgicos alfa Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2003 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperazinas / Piridazinas / Receptores Adrenérgicos alfa 1 / Antagonistas Adrenérgicos alfa Límite: Animals Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2003 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos