Synthesis of fluorine-containing analogues of N-aminoglutethimide

Abstract

Three fluorine-containing analogues of N-aminoglutethimide, a selective inhibitor of the enzyme complex desmolase, have been synthesized. N-Amino-4-fluoro-(3), N-aminopentafluoro-(6), and N-amino-3-trifluoromethyl-glutethimide (8) were all prepared from the corresponding glutethimides [(5), (7), and (9) respectively]via amide hydrazide intermediates, which were thermally cyclised to the target N-aminoglutethimides. That compound (3) was indeed an N-aminoglutethimide was confirmed by an alternative approach, which avoided glutarimide ring cleavage and recyclisation, and instead involved the direct N-amination of the anion derived from 4-fluoroglutethimide (5). Compounds (3), (6), and (8) were all found to be powerful and selective desmolase inhibitors.