SYNTHESIS OF 1-ARYLIMIDAZOLES, A NEW CLASS OF STEROID HYDROXYLATION INHIBITORS

A series of new 1-arylimidazoles has been synthesized and examined for the inhibition of steroid 11β-hydroxylase. Two general synthetic methods used were (a) the nucleophilic displacement of labile aromatic halogen by imidazole and (b) Marckwald's synthesis from an aryl isothiocyanate and amino acetal. The inhibition of steroid 11β-hvdroxylation activity was compared with that of 2-methyl-1,2-bis(3-pyridyl)-1-propanone (metyrapone), and a correlation between structure and activity was discovered for 1-(alkyl-substitut-ed phenyliimidazoles. The presence of bulky ortho substituents increases the activity, 1-(2-t-butylphenyl)imidazole being four times as active as the standard compound. © 1969, American Chemical Society. All rights reserved.