18586-88-4Relevant academic research and scientific papers
Synthesis and in vitro activity of some epimeric 20α-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17α-hydroxylase/c17,20-lyase and 5α-reductase
Ling, Yang-Zhi,Li, Ji-Song,Kato, Katsuya,Liu, Yang,Wang, Xin,Klus, Gregory T.,Marat, Kirk,Nnane, Ivo P.,Brodie, Angela M. H.
, p. 1683 - 1693 (1998)
Some epimeric 20-hydroxy, 20-oxime, 16α, 17α-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17α-hydroxylase/C17,20-lyase (P450(17α)) and 5α-reductase (5α-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereoselectivity for 20β-ol [20α/20β-OH (4α/4β)=1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20α-ol (4αb). The 20α- and 20β-hydroxy-4,16-pregnadien-3-one (9α) and (9β) were synthesized from the alcohols 4αb and 4βb. Several 20-oxime pregnadienes and 16α,17α-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17α,20-aziridine (13b) and 20(R)-17β,20-aziridine (14a). Several compounds inhibited the human P450(17α) with greater potency than ketoconzole. The 5α-R enzyme assay showed that while (9α) did not have any activity, (9β) and (3b) were potent 5α-reductase (IC50=21 and 31nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5α-R (IC50=63 and 115nM, compared to 33nM for finasteride) and P450(17α) (IC50=43 and 25nM, compared to 78nM for ketoconazole). Copyright (C) 1998 Elsevier Science Ltd.
