Stereoselective synthesis of some 17β-dihydrooxazinyl steroids, as novel presumed inhibitors of 17α-hydroxylase-C17,20-lyase

Synthesis and conformational study of P‐heterocyclic androst‐5‐ene derivatives

“…Exhaustive studies have been carried out on substituted monocyclic dioxaphosphorinanes [7,25,26] and monocycle-condensed cyclic phosph(on)ate derivatives [6,[18][19][20][27][28][29] to reveal a conformational flexibility of the hetero ring for P-substitution [8,14,15,[21][22][23]. The specific conformational behavior of these rings has been handled in terms of a chair-alternative boat or a chair-twist equilibrium, and the coupling constants 3 J (H,H) and 3 J (H,P) have been used as indicators of possible dynamic processes [30].…”

“…A number of compounds containing a heterocyclic moiety at position 17β in this series exhibit noteworthy pharmacological effects [13][14][15][16]. Analogous molecules containing a P-ring, however, have not been studied.…”

CYP17 Inhibitors for Prostate Cancer Treatment – An Update

“…6) was less potent than ketoconazole (2) in inhibiting recombinant human CYP17 expressed in E. coli [235]. A series of steroidal dihydrooxazines 141-152 (Scheme 14) were synthesized and tested against rat CYP17 but were found not to display efficient C 17,20 -lyase inhibition when compared to ketoconazole (2) [236]. The lack of activity was suggested to occur due to the bulkiness of the C17 substituent and the lack of a double bond at C16.…”

Characterization of antiproliferative activities of triazolyl-steroid derivatives

“…The synthesis of steroidal heterocycles has also attracted considerable interest in view of their valuable pharmacological activities (Wölfling et al, 2004, Wölfling et al, 2006. Steroidal azoles have been described as potent inhibitors of 17α-hydroxylase-C 17,20 -lyase (CYP17), which can block androgen synthesis at an early stage, and may therefore be of use in the treatment of prostatic carcinoma (Hofmeister et al, 1992, Brodie andNjar, 1999).…”