p-(3-Amino-1-adamantyl)calix [4]arenes with free and alkylated lower rim, representing conjugates of the aminoadamantane pharmacophore fragment and the calixarene platform, were synthesized for the first time by the Curtius rearrangement route starting from p-(3-carboxy-1-adamantyl)calix [4]arenes. The synthesized compounds were evaluated for activity against herpes simplex virus 2 (HSV-2). The nonalkylated compound with free phenol hydroxy groups is the first aminoadamantylcalixarene reported to possess antiviral properties (chemotherapeutic safety index, SI » 12.5). Alkylation at the lower rim of the calixarene platform leads to an increase in cytotoxicity and to the disappearance of anti-HSV activity.Calix[4]arenes (I) represent cyclic metacyclophanes, which are composed of phenol fragments bridged by methylene groups. These compounds have recently received much attention for their ability to serve as receptors of metal ions and neutral molecules, which opens up ways to using them as carriers, sensors, chromatographic media, ligands in homogeneous catalysis, etc.[1].Although the antituberculous activity of p-tert-octylcalix[8]arene modified at the lower rim with poly(oxyethylene) substituents (I with R = tert-octyl, X = (CH 2 CH 2 O) n H, n = 8) was observed as long ago as in 1955 (then it was considered a tetramer) [2 -4], data available on the pharmacological properties of calixarene derivatives are still rather restricted. In 1996, Casnati et al. reported on the antimicrobial activity of vancomycin antibiotic mimetics based on calix[4]arenes modified with dipeptide bridges at the upper rim [5]. Various calixarene derivatives with sulfonate, carboxylate, phosphoryl, and sulfamide groups at the upper rim were patented as antithrombotic [6], antiviral [7 -9], antimicrobial [10], and antibacterial, antifungal, and antitumor [11] agents. Among calix[n]arenes (n = 4, 6, 8), derivatives with R = SO 3 Na, (CH 2 ) m CO 2 H (m = 0 -2), PO 3