Substituted adamantylphthalimides: Synthesis, antiviral and antiproliferative activity

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N‐(4′‐R2)phthalimidoadamantanes (1–7), 3‐[N‐(4′‐R2)phthalimido]‐1‐adamantanols (8–10), and 3‐[N‐(4′‐R2)phthalimido]adamantane‐1‐carboxylic acids (11–15), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH2 substituent at the phthalimide (compounds 3 and 5). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella‐zoster virus was found for compounds 3 and 5, but these compounds lacked selectivity. The results presented are important for the rational design of the next‐generation compounds with anticancer and antiviral activities.

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