Design, synthesis, and evaluation of 4-(4'-aminobenzyl)-2-oxazolidinones as novel inhibitors of the cytochrome P-450 enzyme aromatase.
The synthesis of a series of N-alkylated 4-(4(')aminobenzyl)-2-oxazolidinones is described using a synthetically useful scheme which avoids the use of phosgene-since the derivatization is undertaken with the oxazolidin-2-one ring intact. The compounds were tested for human placental aromatase (AR) inhibition in vitro, using [1beta,2beta-3H]androstenedione as substrate for the AR enzyme. The compounds were found, in general, to be more potent than the standard compound, aminoglutethimide (AG), and as such proved to be good lead compounds in the search for more specific AR inhibitors.
Ahmed
Sabbir
S
School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK. s.ahmed@kingston.ac.uk
Adat
Shaheen
S
Murrells
Annabel
A
Owen
Caroline P
CP
Amanuel
Yonas
Y
D000478:Alkylation; D000735:Androstenedione / Q000737:chemistry; D047072:Aromatase Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D023303:Oxazolidinones; D011084:Polycyclic Aromatic Hydrocarbons; D000735:Androstenedione