Synthesis of 8-chloro-benzo[c]quinolizin-3-ones as potent and selective inhibitors of human steroid 5α-reductase 1

✍ Scribed by Antonio Guarna; Ernesto G. Occhiato; Dina Scarpi; Chiara Zorn; Giovanna Danza; Alessandra Comerci; Rosa Mancina; Mario Serio

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 175 KB
• Volume: 10
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(99)00698-8

✦ Synopsis

AbstractÐThe synthesis of a series of dierently substituted 8-chloro-benzo[c]quinolizin-3-ones, as potent and selective human steroid 5a-reductase type 1 inhibitors, has been accomplished by a four-step procedure based on the TiCl 4 -promoted tandem Mannich±Michael cyclization of 2-silyloxy-1,3-butadienes with N-t-Boc iminium ions from quinolin-2-ones. The presence on the benzo[c]quinolizinone nucleus of a methyl group and a double bond at positions 6 and 4-4a, respectively, as in compound 1d, gave rise to one of the most potent non-steroidal 5aR-1 inhibitors reported so far (IC 50 =14 nM).