Effect of C-Ring Modifications in Benzo[c]quinolizin-3-ones, New Selective Inhibitors of Human 5?-Reductase 1 (Articolo in rivista)

Type
Label
  • Effect of C-Ring Modifications in Benzo[c]quinolizin-3-ones, New Selective Inhibitors of Human 5?-Reductase 1 (Articolo in rivista) (literal)
Anno
  • 2001-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/S0968-0896(01)00012-8 (literal)
Alternative label
  • Guarna, ANTONIO; Occhiato, Ernesto Giovanni; Machetti, Fabrizio; Trabocchi, Andrea; Scarpi, Dina; Danza, Giovanna; Mancina, Rosa; Comerci, A.; Serio, Mario (2001)
    Effect of C-Ring Modifications in Benzo[c]quinolizin-3-ones, New Selective Inhibitors of Human 5?-Reductase 1
    in Bioorganic & medicinal chemistry (Print); Pergamon-Elsevier Science Ltd., Oxford (Regno Unito)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Guarna, ANTONIO; Occhiato, Ernesto Giovanni; Machetti, Fabrizio; Trabocchi, Andrea; Scarpi, Dina; Danza, Giovanna; Mancina, Rosa; Comerci, A.; Serio, Mario (literal)
Pagina inizio
  • 1385 (literal)
Pagina fine
  • 1393 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 9 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 6 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • Scopu (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Centro di studio della chimica e della struttura dei composti eterociclici del CNR, Dipartimento di chimica Organica 'Ugo Schiff' dell'Università di Firenze Dipartimento di fisiopatologia dell'Università di Firenze (literal)
Titolo
  • Effect of C-Ring Modifications in Benzo[c]quinolizin-3-ones, New Selective Inhibitors of Human 5?-Reductase 1 (literal)
Abstract
  • The synthesis and the inhibition potency of octahydro- and decahydrobenzo[c]quinolizin-3-one derivatives 3-7, as new non-steroidal selective inhibitors of human enzyme 5 alpha -reductase type 1, are reported. These compounds differ from the recently reported benzo[c]quinolizin-3-one inhibitors 2 by the presence of a fully or partially saturated C-ring. Compounds 3 and 4, with a double bond in the C-ring, were prepared by sequential rearrangement-annulation of isoxazolines 19 and 20. C-ring saturated compounds 5-7 were prepared by the Lewis acid-promoted Mannich-Michael tandem reaction of Danishefsky diene with the appropriate N-t-Boc iminium ion. Inhibition experiments were carried out on 5 alphaR-1 and 5 alphaR-2 expressed by CHO cells. Among the prepared compounds, octahydrobenzo[c]quinolizin-3-one 3, with a double bond at the position 6a-10a, was a potent and selective inhibitor of human 5 alphaR-1 (IC50 = 58 nM). The introduction of a tert-butylcarboxyamide at the position 8 (compound 4) was deleterious for the inhibition activity. The lack of the double bond in the C-ring reduced strongly the inhibition activity of compounds 5-7. The extended planarity of the most potent benzo[c]quinolizin-3-ones as well as favorable interactions of the C-ring unsaturation with the enzyme active site could account for the inhibition activity of these compounds. (literal)
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