Discovery of Benzyloxyphenyl- and Phenethylphenyl-Imidazole Derivatives As a New Class of Ante–drug Type Boosters

Although cytochrome P450 3A4 (CYP3A4) inhibitors are used as boosters to increase drug absorption, the inhibition of CYP3A4 activity may affect the metabolism of other co-administered drugs. Therefore, we screened for and developed a new class of boosters to improve the oral availability of drugs. We identified benzyloxyphenyl imidazole and phenethylphenyl imidazole derivatives as new types of CYP3A4 inhibitors. Among the compounds synthesized, an ester 5c was found to inhibit CYP activity and the compound 5c was gradually converted to an inactive metabolite 5d under physiological conditions, indicating that the ester 5c may represent a novel ante-drug type booster.