C17,20-Lyase inhibitors I. Structure-based de novo design and SAR study of C17,20-lyase inhibitors

17,20-Lyase inhibitors. Part 3: Design, synthesis, and structure–activity relationships of biphenylylmethylimidazole derivatives as novel 17,20-lyase inhibitors

“…44 During the same period, two studies by Hartmann et al also reported a steroid mimetic approach using a biphenyl ring, 29,30 but our studies were continued independently. 45 The objective of this study was to identify potent 17,20-lyase inhibitors with selectivity over the cytochrome P450 enzymes, particularly CYP3A4, a major drug-metabolizing enzyme.…”

Multistep Continuous-Flow Synthesis of Condensed Benzothiazoles

“…Benzothiophene analogues (9a-c) were also prepared from 2-fluoro-5-nitroacetophenone (8a), 2-fluoro-5-nitrobenzaldehyde (8b), and 2-fluoro-3-nitroacetophenone (8c) with ethyl thioglycolate (for results, see Table 1, entries 4-6, in comparison with batch reactions [16]). We found that compounds 9a-c can be obtained under flow conditions with DIPEA in one step ( Figure 6).…”

Paradigm Shift in the Concept of Hormonal Milieu of Prostate Cancer

“…The compound was found to be selective for CYP17A1 over 11-hydroxylase by an impressive 260-fold, and exhibited suppressive effects on testosterone biosynthesis in rats and reduction in the weight of prostate and seminal vesicles in the rat. [92,93] Orteronel was also capable of reducing serum testosterone levels down to castration level after 8 hours following a single oral administration of 1mg/kg to monkeys. A practical asymmetric synthesis of Orteronel has been established in eight steps from 2,3-dihydroxy naphthalene.…”