365220-63-9Relevant academic research and scientific papers
Effect of C-ring modifications in benzo[c]quinolizin-3-ones, new selective inhibitors of human 5α-reductase 1
Guarna, Antonio,Occhiato, Ernesto G.,Machetti, Fabrizio,Trabocchi, Andrea,Scarpi, Dina,Danza, Giovanna,Mancina, Rosa,Comerci, Alessandra,Serio, Mario
, p. 1385 - 1393 (2001)
The synthesis and the inhibition potency of ocatahydro- and decahydrobenzo[c]quinolizin-3-one derivatives 3-7, as new non-steroidal selective inhibitors of human enzyme 5α-reductase type 1, are reported. These compounds differ from the recently reported enzo[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 in 5αR-1 and 5αR-2 expressed by CHO cells. Among the prepared compounds, octahydrobenzo9c0quinolizin-3-one3, with a double bond at the position 6a-10a, was a potent and selective inhibitor of human 5αR-1 IC50 = 58 nM). The introduction of a tert-butylcarboxyamide at the position 8 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. Copyright
