2. Academic Validation
  3. Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D(3)

Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D(3)

  • J Med Chem. 2004 Dec 30;47(27):6854-63. doi: 10.1021/jm040129+.
Mehmet Kahraman 1,  Sandra Sinishtaj,  Patrick M Dolan,  Thomas W Kensler,  Sara Peleg,  Uttam Saha,  Samuel S Chuang,  Galina Bernstein,  Bozena Korczak,  Gary H Posner
Affiliations

Affiliation

  • 1 Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA.
PMID: 15615534 DOI: 10.1021/jm040129+
Abstract

A dozen 24-sulfoximine analogues of the hormone 1alpha,25-dihydroxyvitamin D(3) 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 (IC(50) = 7.4 nM) having low calcemic activity. In addition, this compound shows high selectivity toward the CYP24 enzyme in comparison to CYP27A1 (IC(50) > 1000 nM) and CYP27B (IC(50) = 554 nM).

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