On July 24, 1992, Rotstein, David M.; Kertesz, Denis J.; Walker, Keith A. M.; Swinney, David C. published an article.COA of Formula: C12H16N2O2 The title of the article was Stereoisomers of ketoconazole: preparation and biological activity. And the article contained the following:
The four stereoisomers of the antifungal agent ketoconazole, (2S,4R)-, (2R,4R)-, (2R,4S)-, and (2S,4S)-(imidazolylmethyl)phenyl{[(acetylpiperazinyl)phenoxy]methyl}dioxolanes I, were prepared and evaluated for their selectivity in inhibiting a number of cytochrome P 450 enzymes. Thus, (bromomethyl)phenyldioxolanes II condensed with 4-(N-acetylpiperazino)phenol and imidazole to give I. II were prepared by bromination of 2′,4′-dichloroacetophenone followed by reaction with (S)- and (R)-solketal tosylate. Large differences in selectivity among the isomers were observed for inhibition of the cytochromes P 450 involved in steroid biosynthesis, whereas little difference was observed for inhibition of those associated with hepatic drug metabolism The cis-(2S,4R) and trans-(2R,4R) isomers are equipotent in inhibiting corticoid 11β-hydroxylase and much more effective than their antipodes. Little selectivity was observed for inhibition of cholesterol side chain cleavage or xenobiotic hydroxylases. These data indicate that the affinity of azoles for cytochrome P 450 enzymes involved in steroid synthesis is high dependent on the stereochem. of the entire mol., whereas binding to drug metabolizing enzymes is a less selective process. The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).COA of Formula: C12H16N2O2
The Article related to ketoconazole stereoisomer preparation cytochrome p450 inhibition, imidazolylmethylphenylacetylpiperazinylphenoxymethyldioxolane preparation cytochrome p450 enzyme inhibition and other aspects.COA of Formula: C12H16N2O2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics