Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides.
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.
Aboraia
Ahmed S
AS
Medicinal Chemistry, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
Yee
Sook Wah
SW
Gomaa
Mohamed Sayed
MS
Shah
Nikhil
N
Robotham
Anna C
AC
Makowski
Bart
B
Prosser
David
D
Brancale
Andrea
A
Jones
Glenville
G
Simons
Claire
C
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
D000577:Amides; D001572:Benzofurans; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase