Synthesis and Antiviral Activity of N-Acyl Derivatives of 4,6-Di-( tert -butyl)-2-aminophenol

Abstract

In recent years, the results of a number of experimental and clinical investigations have shown that antioxidants are promising candidates in the group of drugs used for the treatment of viral pathologies. The inhibiting action of antioxidants with respect to viral replication was reported for herpes simplex virus (HSV), hepatitis C, Epstein – Barr virus, cytomegalic inclusion virus, etc. [1]. It was also demonstrated that phenolic antioxidants of plant origin reduce HIV expression in tests on cell cultures [2]. In this context, we have undertaken the search for viral inhibitors among aminophenol derivatives known to be capable of controlling the generation and utilization of free radicals [3]. Previously [4], we described the synthesis of N-acyl-substituted 4,6-di-tert-butyl-2-aminophenols and reported on the results of pharmacological tests revealing sufficiently high anti-HSV activity in some of the synthesized compounds. In continuation of this search for new antiviral agents in the class of spatially constrained o-aminophenol, we have synthesized a series of N-aryl and N-cycloalkyl derivatives of 4,6-di-tert-butyl-2-aminophenol and tested these compounds for antiviral activity with respect to HSV and influenza species in cell cultures. The target compounds (I – VI) were synthesized by treating 3,5-di-tert-butylpyrocatechol with aniline, its derivatives, and cyclohexylamine in petroleum ether or methanol.