A dozen 24-sulfoximine analogues of the hormone 1α,25- dihydroxyvitamin D3 were prepared, differing not only at the stereogenic sulfoximine stereocenter but also at the A-ring. Although these sulfoximines were not active transcriptionally and were only very weakly antiproliferative, some of them are powerful hydroxylase enzyme inhibitors. Specifically, 24-(S)-NH phenyl sulfoximine 3a is an extremely potent CYP24 inhibitor (IC50 = 7.4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC50 > 1000 nM) and CYP27B (IC50 = 554 nM).
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of medicinal chemistry|
|State||Published - Dec 30 2004|
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery