title: Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides.
abstract: A series of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides were prepared, using an efficient three- to five-step synthesis, and evaluated for their inhibitory activity against human cytochrome P450C24A1 (CYP24A1) hydroxylase. Inhibition ranged from IC50 0.3-72 microM compared with the standard ketoconazole IC50 0.52 microM, with the styryl derivative (11c) displaying enhanced activity (IC50=0.3 microM) compared with the standard, providing a useful preliminary lead for drug development.
authors.affiliation: Medicinal Chemistry, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Aboraia
authors.forename: Sook Wah
authors.initials: SW
authors.lastname: Yee
authors.forename: Mohamed Sayed
authors.initials: MS
authors.lastname: Gomaa
authors.forename: Nikhil
authors.initials: N
authors.lastname: Shah
authors.forename: Anna C
authors.initials: AC
authors.lastname: Robotham
authors.forename: Bart
authors.initials: B
authors.lastname: Makowski
authors.forename: David
authors.initials: D
authors.lastname: Prosser
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Glenville
authors.initials: G
authors.lastname: Jones
authors.forename: Claire
authors.initials: C
authors.lastname: Simons
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D000577:Amides; D001572:Benzofurans; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase