Synthesis and CYP24 inhibitory activity of 2-substituted-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives

Sook Wah Yee; Claire Simons

doi:10.1016/j.bmcl.2004.08.040

Synthesis and CYP24 inhibitory activity of 2-substituted-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5651-4. doi: 10.1016/j.bmcl.2004.08.040.

Authors

Sook Wah Yee¹, Claire Simons

Affiliation

¹ Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, Wales, UK.

PMID: 15482941
DOI: 10.1016/j.bmcl.2004.08.040

Abstract

The synthesis of novel 2-benzyl- and 2-benzylidene-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives and their inhibitory activity versus kidney mitochondrial 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24) is described. The 2-benzylidenetetralone derivatives were found to be very weak inhibitors (IC(50) 20 >100 microM), whereas the 2-benzyltetralone derivatives showed promising inhibitory activity (IC(50) 0.9 microM for the most active derivative) compared with ketoconazole (IC(50) 20 microM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytochrome P-450 Enzyme Inhibitors*
Cytochrome P-450 Enzyme System / chemistry
Humans
Molecular Structure
Steroid Hydroxylases / antagonists & inhibitors*
Steroid Hydroxylases / chemistry
Structure-Activity Relationship
Tetralones / chemical synthesis*
Tetralones / pharmacology*
Vitamin D3 24-Hydroxylase

Substances

Cytochrome P-450 Enzyme Inhibitors
Tetralones
Cytochrome P-450 Enzyme System
Steroid Hydroxylases
Vitamin D3 24-Hydroxylase